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Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO (AIM-NIVO)
McFadden, Faith - mcfaddenfr@vcu.edu
Poklepovic, Andrew, S
NCT03816345
HM20022009
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab or other PD1/PD-L1 inhibitors are FDA-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)
* Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
* WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation, or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
* These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
* Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. Patients can resume treatment upon termination of a pregnancy or the completion of a successful pregnancy
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort (Please note: Patients with more than one autoimmune disease should receive assessments for all previously diagnosed autoimmune diseases. For example, a patient with psoriasis and IBD might be enrolled in the IBD cohort. Disease assessments for both psoriasis and IBD should be obtained, as per protocol. Case report forms \[CRFs\] for all relevant autoimmune diseases should be utilized. However, all additional cohort requirements will be considered optional and only the assessments from the assigned cohort will be considered mandatory)
* DM/SSc-SPECIFIC INCLUSION: Patients with known SSc or DM according to updated classification criteria (Van den Hoogan et al., Arthritis Rheum 2013;65(11):2737-47; Lundberg et al., A\&R in press). Overlap features are permitted, but patients must meet criteria for a "primary diagnosis" of DM or SSc
* DM/SSc-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for DM or SSc unless specifically excluded
* DM/SSc-SPECIFIC INCLUSION: Patients must have a baseline computed tomography (CT) of the chest (within 6 months of study entry)
* RA-SPECIFIC INCLUSION: Rheumatologist-diagnosed RA requiring prior treatment with disease-modifying antirheumatic drugs (DMARDs) before patient was diagnosed with current malignancy. We recommend, but do not require, documentation for meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
* RA-SPECIFIC INCLUSION: Prednisone up to 10 mg/day will be allowed. Intraarticular steroids will be allowed for the treatment of new symptomatic joints
* RA-SPECIFIC INCLUSION: Nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed
* SLE-SPECIFIC INCLUSION: SLE diagnosed by a rheumatologist. The patient should meet the revised 1997 American College of Rheumatology (ACR) classification criteria for SLE, but this is not mandatory
* ULCERATIVE COLITIS (UC)-SPECIFIC INCLUSION: Diagnosis of UC must be made by endoscopy with biopsies
* UC-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* UC-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (antigen \[Ag\] negative, antibody \[core (c)Ab\] negative, antibody \[surface (s)Ab\] positive or negative) and Mycobacterium tuberculosis (purified-protein- derivative \[PPD\] or enzyme-linked immunospot assay \[ELISpot or T-spot\]) or be on appropriate anti-microbial treatment for these infections
* UC-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission, defined as a Mayo Clinic score (MCS) of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 either without medications, or treated with 5-ASA derivative, probiotic, or prior fecal transplant
* UC-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on 6-mercaptopurine, azathioprine, methotrexate, or rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* UC-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either be A) in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on a biologic therapy targeting tumor necrosis alpha (TNF-α) (infliximab, adalimumab, golimumab), α4β7 integrin (vedolizumab), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease defined as a MCS of 3-5 and no subscore higher than 2, and an endoscopic subscore of \< 2 on one of the medications or combination of medications defined for the Moderate or Mild cohort
* CROHN'S DISEASE (CD)-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* CD-SPECIFIC INCLUSION: If patients have prior known disease in the stomach or small intestines, appropriate endoscopic evaluation (esophagogastroduodenoscopy/video capsule endoscopy) and/or imaging (computed tomography or magnetic resonance enterography) must also be current within 4 weeks prior to nivolumab administration
* CD-SPECIFIC INCLUSION: Deep enteroscopy techniques, such as double balloon enteroscopy, will not be required
* CD-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (sAg negative, cAb negative, sAb positive or negative) and M. tuberculosis (PPD or ELISpot or T-spot) or be on appropriate anti-microbial treatment for these infections
* CD-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission as defined by a Crohn's Disease Activity Index (CDAI) \< 150 either without treatment or on a 5-ASA derivative, probiotic, antibiotics, or following fecal transplant
* CD-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission as defined by a CDAI \< 150 on 6-mercaptopurine, azathioprine, methotrexate, rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* CD-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either A) be in clinical remission as defined by a CDAI \< 150 on biologic therapy targeting TNF-α (infliximab, adalimumab, certolizumab pegol), IL-12/23p40 (ustekinumab), α4β7 integrin (vedolizumab), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease as defined by a CDAI of 150 to 220 on one of medications or combination of medications defined for the Moderate or Mild cohort
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For other autoimmune diseases that cannot be classified, the eligibility criteria will be determined by the managing rheumatologist or other autoimmune disease specialist, based on the clinical judgement and current American College of Radiology (ACR) classification guidelines or other relevant guidelines, as per the disease category in question
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For giant cell arteritis (GCA), patients must have had positive temporal artery biopsy for GCA and abnormal erythrocyte sedimentation rate (ESR) at time of diagnosis
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For polymyalgia rheumatica (PMR), patients must have clinical diagnosis in addition to elevated inflammatory markers including (ESR, C reactive protein \[CRP\])
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: Patients can be in remission (with no glucocorticoids or immunosuppressive medications) or have low-moderate activity, which is defined as being on prednisone ≤ 10 mg or equivalent
* MS-SPECIFIC INCLUSION: Patients must meet 2017 McDonald criteria for the diagnosis of MS (Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol. 17(2):162-173.)
* MS-SPECIFIC INCLUSION: Patients with MS can be in remission and can have a history of being on immunomodulatory agents, but at the time of entry into the clinical trial, patients should be off any concurrent MS therapy for at least 2 weeks. Patients receiving concomitant interferon gamma (IFN-γ treatment) will be permitted in the study
* SJS-SPECIFIC INCLUSION: SjS diagnosed by a rheumatologist or oral medicine provider. The patient should meet the American-European Consensus Criteria for Sjögren's Syndrome (Vitali, et al., 2002). If on treatment, the patient may only be on hydroxychloroquine and prednisone ≤ 10 mg or equivalent
* PSO/PSA-SPECIFIC INCLUSION: Patients with known PsO as diagnosed by a dermatologist or PsA by a rheumatologist and/or by Classification for Psoriatic Arthritis (CASPAR) criteria (Tillett et al., 2012)
* PSO/PSA-SPECIFIC INCLUSION: Patients must have stable disease as determined by the investigator with no change in systemic therapy and/or biologic therapy for at least 3 months, except for those on tumor necrosis factor (TNF) inhibitors. In the case of TNF inhibition, patients may have transitioned to an alternative biologic therapy with stable disease for at least 4 weeks. For PsA, no change in corticosteroid therapy for at least 1 month prior to baseline and dose must be 10 mg or less
* PSO/PSA-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for PsO or PsA unless specifically excluded
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* UC-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* UC-SPECIFIC EXCLUSION: Prior colectomy
* UC-SPECIFIC EXCLUSION: Concurrent primary sclerosing cholangitis (PSC). Patients with PSC can be enrolled on the Other Autoimmune Diseases Cohorts
* UC-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* CD-SPECIFIC EXCLUSION: Known untreated abscesses, untreated and symptomatic strictures, short gut physiology, or isolated jejunal disease
* CD-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* CD-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* MS-SPECIFIC EXCLUSION: Patients with MS cannot have medical contraindications to gadolinium-enhanced magnetic resonance imaging (MRI) PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib, DRUG: Fluoropyrimidine, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab, DRUG: Platinum Compound, DRUG: Platinum Doublet
Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm, Multiple Sclerosis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sjogren Syndrome, Systemic Lupus Erythematosus, Systemic Scleroderma, Ulcerative Colitis
Nonconforming Lisocabtagene Maraleucel Expanded Access Protocol
Hall, Charles, E. - hallce3@vcu.edu
Simmons, Gary, L.
NCT04400591
HM20022052
Inclusion Criteria:
• Subject and/or LAR must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
• Subject has relapsed and/or refractory large B-cell lymphoma and is, per the treating physician assessment, eligible for treatment with lisocabtagene maraleucel per the approved prescribing information.
• Subject is ? 18 years of age at the time of signing the informed consent form.
• Subject had a specific batch of lisocabtagene maraleucel manufactured intended for commercial treatment; however, the final manufactured product did not meet commercial release criteria.
• Remanufacturing (eg, repeat leukapheresis and manufacturing) is deemed not feasible or clinically inappropriate per assessment of the treating physician in discussion with the subject.
• Subject is clinically stable, has recovered from any toxicities prior to receiving lymphodepleting chemotherapy, and has adequate bone marrow function to receive lymphodepleting chemotherapy. The treating physician is advised to contact Medical Monitor in the event there is any concern regarding administration of lymphodepleting chemotherapy.
• Females of childbearing potential must:
• Have a negative pregnancy test as verified by the treating physician within 7 days prior to the first dose of lymphodepleting chemotherapy following institutional testing methodology practices. This applies even if the subject practices true abstinence from heterosexual contact.
• Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective method from screening until at least 12 months after the nonconforming lisocabtagene maraleucel administration.
• Agree to abstain from breastfeeding during study participation and for at least 12 months following nonconforming lisocabtagene maraleucel administration.
• There are insufficient exposure data to provide any recommendation concerning the duration of contraception and the abstaining from breastfeeding following treatment with lisocabtagene maraleucel. Any decision regarding contraception and breastfeeding after infusion should be discussed with the treating physician.
• Male subjects must:
• Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 12 months after nonconforming lisocabtagene maraleucel administration even if the subject has undergone a successful vasectomy.
• There are insufficient exposure data to provide any recommendation concerning the duration of contraception following treatment with lisocabtagene maraleucel. Any decision regarding contraception after infusion should be discussed with the treating physician
• Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells for usage in other individuals for at least 1 year following nonconforming lisocabtagene maraleucel administration.
Exclusion Criteria:
• Subject has a hypersensitivity to the active substance or to any of the excipients.
• Subject should not experience a significant worsening in clinical status that would, in the opinion of the treating physician, either increase the risk of adverse events associated with lymphodepleting chemotherapy, or exclude them from treatment with nonconforming lisocabtagene maraleucel.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness, sociologic or geographic condition that would prevent the subject from participating in the Expanded Access Protocol complying with protocol requirements in the Investigator's judgement.
• Subject has any condition and/or laboratory abnormality that places the subject at unacceptable risk if he/she were to participate in the Expanded Access Protocol based on the Investigator's judgement
• Pregnant or nursing women or has intention of becoming pregnant during the study.
• Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study).
• Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of pretreatment evaluation
• Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of nonconforming lisocabtagene maraleucel administration.
• Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD)
• Use of the following:
• Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 72 hours prior to nonconforming lisocabtagene maraleucel administration. Physiologic replacement, topical, and inhaled steroids are permitted.
• Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ? 300 mg/m2)given after leukapheresis to maintain disease control must be stopped ? 7 days prior to lymphodepleting chemotherapy.
• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of LD chemotherapy. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to lymphodepleting chemotherapy.
• Donor lymphocyte infusions within 6 weeks of nonconforming lisocabtagene maraleucel administration.
Biological: Nonconforming Lisocabtagene Maraleucel
Lymphoma, Large B-Cell, Diffuse
Expanded Access, JCAR017, Lisocabtagene Maraleucel, CAR T, nonconforming,, relapsed/refractory diffuse large B cell lymphoma, nonconforming lisocabtagene mareleucel
Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma
Schaefer, Melissa - schaeferm@vcu.edu
Alesi, Erin, R.
NCT04671667
HM20022077
Inclusion Criteria:
* Patient must be between 18 and 79 years of age
* Patient must have locoregionally recurrent or second primary HNSCC (oral cavity, oropharynx, larynx, hypopharynx) in a previously radiated field
* Patient must have undergone surgery with gross total resection and must be randomized within 8 weeks of surgery
* Patients must have high risk disease defined as:
* Positive margins and/or extra nodal extension (ENE)
* Positive margins are defined as malignancy at or within 1 mm of the margin. High grade dysplasia (i.e. carcinoma in situ) at the margin is also considered positive
* ENE may be either gross or microscopic
* Patient must have a PD-L1 Combined Positive Score (CPS) \>= 1 in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Testing can be done locally as long as it is done in a CLIA certified laboratory. This testing must be on the tumor specimen from the resection of the patient's recurrent or second primary HNSCC
* Patient must have had prior radiation to the area of recurrent or second primary tumor. This is defined as \> 50% of the presurgical tumor volume having previously received a dose of \> 45 Gy as determined by the treating radiation oncologist
* Patient must have completed prior radiation a minimum of 6 months prior to randomization
* Patient must not have any evidence of distant disease based on baseline imaging done within 28 days prior to randomization
* Patient must not have received anti-PD-1/PD-L1 therapy for recurrent disease. If the patient received anti-PD-1/PD-L1 therapy as part of initial upfront curative intent treatment (either as part of definitive non-surgical therapy or in the adjuvant setting) in the past, the last dosage of anti-PD-1/PD-L1 therapy must have been given greater than one year prior to randomization
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab or chemotherapy if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A patient of childbearing potential is someone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on study treatment, and continue for 120 days after the last dose of study treatment
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 28 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 28 days prior to protocol randomization)
* Creatinine clearance \> 30 ml/min using the Cockcroft-Gault formula (obtained =\< 28 days prior to protocol randomization)
* Patient must not have a current active infection that requires systemic treatment at time of randomization
* Patient must not have a history of non-infectious pneumonitis requiring steroids within 3 years prior to randomization
* Patient must not have a history of solid organ transplant or stem cell transplant
* Patient must not be on immunosuppressive medication within 7 days prior to randomization, EXCEPT for the following: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. Patients with New York Heart Association class III or IV heart failure are not eligible
* Patient must not have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed
* Patient must not have severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
* Patient must not have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as they have not been HIV-infected with a history of Kaposi sarcoma and/or multicentric Castleman disease
* Patient must not have a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
* NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Pembrolizumab, RADIATION: Proton Beam Radiation Therapy
Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 3
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04916340
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency BEHAVIORAL: Muscular Strength Training Group, BEHAVIORAL: Muscular Fitness Training Group
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 1
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04916327
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency DIETARY_SUPPLEMENT: Antioxidant, DIETARY_SUPPLEMENT: Placebo
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
Study of Immune Globulin Intravenous (Human) GC5107 in Pediatric Subjects With Primary Humoral Immunodeficiency
Hyejoo Kim - hyejoo.kim@gccorp.com
Zhao, Wei
NCT04565015
HM20021702
Inclusion Criteria:
• Subject must be ≥ 2 to < 17 years of age, at the time of signing the informed consent
• Pediatric subject has a confirmed and documented clinical diagnosis of Primary Humoral Immunodeficiency, including hypogammaglobulinemia or agammaglobulinemia
• Subject who has received 300 - 900 mg/kg of IGIV therapy at 21 or 28 day intervals for at least 3 months prior to this study
• Subject who has at least 2 documented plasma IgG trough level of ≥ 500 mg/dL at two infusion cycles (21 or 28 days) within 12 months prior to enrollment
• Subject who is willing to comply with all requirements of the protocol
Exclusion Criteria:
• Subject who has a history of clinically significant reactions or hypersensitivity to IGIV or other injectable forms of IgG
• Subject who has IgA deficiency and is known to have antibodies to IgA
• Subject who has secondary immunodeficiency
• Subject who has participated in another clinical study (other than an IGIV study) within 3 weeks prior to screening
• Subject who has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency or isolated IgA deficiency, or who has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
• Subject who has received blood products other than human albumin or human immune globulin within 6 months prior to enrollment
Biological: GC5107
Primary Immune Deficiency
A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV) (DAISY)
Study Contact - JNJ.CT@sylogent.com
NCT04583280
Inclusion criteria:
• The participant weighs within greater than or equal to (>=) 2.4 kilograms (kg) and less than or equal to (<=) 24.6 kg
• Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
• The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as <75 percent [%] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility
• The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
• Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease Exclusion criteria:
• The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
• Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
• Known personal or family history of Long QT Syndrome or sudden cardiac death
• Presence of repetitive ventricular premature contractions (>10/minutes [min]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening
• The participant weighs within greater than or equal to (>=) 2.4 kilograms (kg) and less than or equal to (<=) 24.6 kg
• Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
• The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as <75 percent [%] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility
• The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
• Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease Exclusion criteria:
• The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
• Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
• Known personal or family history of Long QT Syndrome or sudden cardiac death
• Presence of repetitive ventricular premature contractions (>10/minutes [min]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening
Drug: Rilematovir, Drug: Rilematovir X mg/kg, Drug: Placebo
Respiratory Tract Infections
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 2
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04922762
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency BEHAVIORAL: Moderate Intensity, Normal Volume Exercise Training, BEHAVIORAL: High Intensity, Normal Volume Exercise Training, BEHAVIORAL: Moderate Intensity, High Volume Exercise Training
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes
Medical Information - medicalinfo@vrtx.com
Levy, Marlon
NCT04786262
HM20021228
Key
Inclusion Criteria:
* Clinical history of T1D with \> 5 years of duration of insulin dependence
* At least two episodes of documented severe hypoglycemia in the 12 months prior to enrollment
* Stable diabetic treatment
* Consistent use of continuous glucose monitor (CGM) for at least 3 months before Screening and willingness to use CGM for the duration of the study
Key Exclusion Criteria:
-Prior islet cell transplant, organ transplant, or cell therapy
Other protocol defined Inclusion/Exclusion criteria may apply BIOLOGICAL: VX-880
Diabetes Mellitus, Type 1, Impaired Hypoglycemic Awareness, Severe Hypoglycemia
A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1)
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or - ClinicalTrials.gov@lilly.com
Koch, William, C
NCT04427501
HM20022495
Inclusion Criteria:
• Are currently not hospitalized. (Not applicable to participants in treatment arm 22.)
• Have one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion. (Not applicable to participants in treatment arm 22.)
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are males or females, including pregnant females who agree to contraceptive requirements
• Understand and agree to comply with planned study procedures
• Agree to the collection of nasopharyngeal swabs and venous blood. (Not applicable to participants in treatment arms 20-21.)
• The participant or legally authorized representative give signed informed consent and/or assent Participants in treatment arms 7-9, 13-14, and 18-21 ONLY
• Are greater than or equal to (≥)18 years of age and must satisfy at least one of the following at the time of screening
• Are pregnant
• Are ≥65 years of age
• Have a body mass index (BMI) ≥35
• Have chronic kidney disease (CKD)
• Have type 1 or type 2 diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment or
• Are ≥55 years of age AND have:
• cardiovascular disease (CVD), OR
• hypertension, OR
• chronic obstructive pulmonary disease (COPD) or other chronic respiratory disease
• Are 12-17 years of age (inclusive) AND satisfy at least one of the following at the time of screening
• Are pregnant
• Have a body mass index (BMI) ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
• Have sickle cell disease
• Have congenital or acquired heart disease
• Have neurodevelopmental disorders, for example, cerebral palsy
• Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
• Have asthma or reactive airway or other chronic respiratory disease that requires daily medication for control
• Have type 1 or type 2 diabetes
• Have chronic kidney disease
• Have immunosuppressive disease, or
• Are currently receiving immunosuppressive treatment Participants in treatment arm 22 ONLY
• Are 0 (≥ 32 weeks gestational age AND ≥ 1.5 kilograms [kg]) to 17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening
• Are pregnant
• Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
• Have sickle cell disease
• Have congenital or acquired heart disease
• Have neurodevelopmental disorders, for example, cerebral palsy, autism, or Down syndrome (FAIR Health 2020; Spreat et al. 2020)
• Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
• Have asthma, cystic fibrosis, reactive airways disease or other chronic respiratory disease that requires daily medication for control
• Have type 1 or type 2 diabetes
• Have chronic kidney disease
• Have immunosuppressive disease, or
• Are currently receiving immunosuppressive treatment, or
• Are less than (<) one year of age.
• Have one or more COVID-19 symptoms
• Shortness of breath/difficulty breathing
• Fever
• Sore throat
• Nausea
• Diarrhea
• Tiredness
• Headache
• New loss of taste
• Nasal congestion/runny nose
• Chills
• Stomachache
• Vomiting
• Cough
• Muscle/body aches and pain
• New loss of smell
• Poor appetite or poor feeding (in babies) Participants in treatment arm 23 ONLY: Must have first positive result sample of current SARS-CoV-2 viral infection ≤3 days prior to start of treatment administration. Participant can have COVID previously and still meet criteria for this addendum. Positive result needs to be from a current infection. Are 0 (≥ 38 weeks gestational age and ≥ 3.3 kg) to <12 years of age at the time of screening, or are 12 to 17 and weighing <40 kg; and
• Have mild to moderate COVID-19 disease, including one or more COVID-19 symptoms within the last 7 days
• Shortness of breath/difficulty breathing
• Fever
• Sore throat
• Nausea
• Diarrhea
• Tiredness
• Headache
• New loss of taste
• Nasal congestion/runny nose
• Chills
• Malaise
• Vomiting
• Cough
• Muscle/body aches and pain
• New loss of smell
• Poor appetite or poor feeding (in babies under 1 year old)
Exclusion Criteria:
• Have oxygen saturation (SpO2) less than or equal to (≤)93 percent (%) on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) less than (<)300, respiratory rate greater than or equal to (≥)30 per minute, heart rate ≥125 per minute due to COVID-19
• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
• Have known allergies to any of the components used in the formulation of the interventions
• Have hemodynamic instability requiring use of pressors within 24 hours of randomization
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
• Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 29 days
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study
• Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study
• Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
• Have received treatment with a SARS-CoV-2 specific monoclonal antibody
• Have received convalescent COVID-19 plasma treatment
• Have participated in a previous SARS-CoV-2 vaccine study or have received a SARS-CoV-2 vaccine
• Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Mothers who are breast feeding Participants in Treatment Arm 22 ONLY
• Have a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) in the opinion of the investigator
• Are currently hospitalized for treatment of COVID-19. Other reasons for hospitalization are acceptable. Participants in treatment arm 23 ONLY
• SpO2 ≤ 93% on room air at sea level, or while on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity, respiratory rate ≥30 per minute, and heart rate ≥125 per minute due to COVID-19 (FDA February 2021)
• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
• Have known allergies to any of the components used in the formulation of the interventions
• Have hemodynamic instability requiring use of pressors within 24 hours of randomization
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
• Have any co-morbidity requiring surgery within 7 days, or that is considered life-threatening within 29 days
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study.
• Have received treatment with a SARS-CoV-2 specific monoclonal antibody or remdesivir within 90 days before dosing.
• Have received convalescent COVID-19 plasma treatment within 90 days before dosing
• Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Are currently pregnant or breast feeding
Drug: LY3819253, Drug: LY3832479, Drug: LY3853113, Drug: Placebo
COVID-19
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial (EQUATE)
Lantis, Kristin - kllantis@vcu.edu
Yazbeck, Victor, Y
NCT04566328
HM20022350
Inclusion Criteria:
* STEP 0 - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
* STEP 0 - Patient must have newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria
* STEP 0 - Patient must agree to register to the mandatory REVLIMID Risk Evaluation and Mitigation Strategy (RevREMS) program and be willing and able to comply with the requirements of RevREMS
* STEP 0 - Patient must be able to undergo diagnostic bone marrow aspirate following preregistration.
* NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies for clonoSEQ Assay
* NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from the Clonality (ID) test within fourteen (14) days of receipt and reconciliation of fresh bone marrow specimen to the submitting institution
* STEP 1 - Patient must meet all eligibility criteria in STEP 0 with exception of allergy requirement
* STEP 1 - Institution must have received the Clonality (ID) test results from Adaptive Biotechnologies and dominant sequences were identified
* STEP 1 - Patient must have standard risk MM as defined by the Revised International Staging System (RISS) stage I or II
* NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH). Presence of del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these, including any other findings, are standard risk
* R-ISS stage
* Stage I: ISS stage I \[beta2 macroglobulin \< 3.5 mg/L, albumin \> 3.5 g/dL\] AND standard-risk CA AND normal LDH
* Stage II: Not R-ISS stage I or III
* Stage III: ISS stage III \[beta2 macroglobulin \> 5.5 mg/L\] AND high-risk CA OR high LDH (\> upper limit of normal) \[patients with stage III are ineligible\]
* STEP 1 - Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to registration:
* \>= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
* \>= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis
* Involved free light chain \>= 10 mg/dL or \>= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (\< 0.26 or \> 1.65)
* Monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease)
* STEP 1 - Patients must have a serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28 days prior to registration. In addition, a bone marrow biopsy and/or aspirate is required within 28 days if bone marrow is being followed for response
* NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is \>= 200 mg/24 hr. Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response
* NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine. Measurable disease in the serum is defined as having a serum M-spike \>= 1 g/dL. Measurable disease in the urine is defined as having a urine M-spike \>= 200 mg/24 hr
* STEP 1 - Calculated creatinine clearance \> 30 mL/min (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Untransfused platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Patient must have received no more than one cycle (28 days or less) of prior chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided there are no residual toxicity related to radiation and blood counts meet the study requirements. Radiation treatment must be completed at least 14 days prior to Step 1 registration
* STEP 1 - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* STEP 1 - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1 - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1 - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* STEP 1 - Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Patients must not have evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within 6 months prior to Step 1 registration
* STEP 1 - Patient may have a history of current or previous deep vein thrombosis (DVT) or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
* STEP 1 - Patients with a history of chronic obstructive pulmonary disease (COPD) must have FEV1 testing done within 28 days prior to Step 1 registration and the forced expiratory volume in 1 second (FEV1) must be \> 50% of predicted normal
* STEP 2 - Institution must have received Tracking (MRD) test results from Adaptive Biotechnologies
* STEP 2 - Patient must have completed the Step 1 Induction phase of this protocol without experiencing progression
* STEP 2 - Patient must be registered to Step 2 within 8 weeks of completing Step 1 Induction Treatment, counting from last day of completion of last cycle
* STEP 2 - Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
* STEP 2 - Any adverse event(s) related to Step 1 Induction Treatment must have resolved to grade 2 or less
* STEP 2 - Hemoglobin \>= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Platelet count \>= 50,000/mm\^3 (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Calculated creatinine clearance \>= 30 mL/min (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Total bilirubin =\< 1.5 x ULN (Institutional upper limit of normal) (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - ALT and AST \< 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
* STEP 0 - Patient must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products
* STEP 1 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 1 registration to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point,
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* STEP 1 - Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception (for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment
* STEP 1 - Patient must not have peripheral neuropathy \>= grade 2 on clinical examination or grade 1 with pain at time of Step 1 registration
* STEP 1 - Patient must not have any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
* STEP 1 - Patient must not have moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
* NOTE: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to register
* STEP 1 - Patient must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol
* NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* STEP 2 - Patient must not have received any non-protocol therapy outside of the assigned Step 1 Induction treatment including stem cell transplant
* STEP 2 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point,
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* STEP 2 - Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception (for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment DRUG: Bortezomib, BIOLOGICAL: Daratumumab and Hyaluronidase-fihj, DRUG: Dexamethasone, DRUG: Lenalidomide, OTHER: Quality-of-Life Assessment
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma
Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
Megan Scott - bmtctn1904@emmes.com
NCT04965597
Inclusion Criteria:
• Patient must be >= 1.0 year of age and less than 50.0 years of age at the time of enrollment (i.e. patient must have celebrated their 1st birthday when enrolled and must NOT have celebrated their 50th birthday when enrolled; 49.99 years)
• Underlying BMFD treatable by allogenic HCT
• Shwachman-Diamond syndrome
• Criteria for Diagnosis:
• A pathogenic mutation(s) for Shwachman-Diamond syndrome
• For those patients tested but lacking a genetic mutation they must meet both **** criteria below:
• Exocrine pancreatic dysfunction as defined by at least one of the following:
• Pancreatic isoamylase below normal (age >= 3 years old), OR
• Fecal elastase < 200, AND
• Bone marrow failure as evidence by at least one of the following:
• Intermittent or persistent neutropenia (absolute neutrophil count < 1,500/uL), OR
• Hypo-productive anemia with a hemoglobin concentration below the age-related adjusted norms, OR
• Unexplained macrocytosis, OR
• Platelet count < 150,000/uL without alternative etiology, OR
• Hypocellular bone marrow
• Indications for HCT:
• Severe neutropenia (absolute neutrophil count [ANC] < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 eligibility review committee (ERC). In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet the indications for transplant listed above
• Diamond Blackfan Anemia
• Criteria for Diagnosis:
• A pathogenic mutation for Diamond Blackfan anemia
• For those patients tested but lacking a genetic mutation the patient must meet the first *** criteria and at least one of the subsequent *** criteria listed below:
• History of deficiency of erythroid precursors in an otherwise cellular bone marrow AND,
• Reticulocytopenia, OR
• Elevated adenosine deaminase activity, OR
• Elevated hemoglobin F, OR
• Macrocytosis, OR
• Congenital anomalies
• Indications for HCT:
• Red blood cell (RBC) transfusion dependent anemia despite an adequate trial of steroids; OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Congenital Sideroblastic anemia
• Criteria for Diagnosis:
• A pathogenic mutation(s) for sideroblastic anemia
• For those patients tested but lacking a genetic mutation:
• Presence of ringed sideroblasts in the bone marrow excluding acquired causes of ringed sideroblasts such as lead poisoning & zinc toxicity
• Indications for HCT:
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• GATA2 mutation with associated marrow failure
• Criteria for Diagnosis: ** A pathogenic mutation(s) for GATA2
• Indications for HCT:
• Severe neutropenia (ANC < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC. In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet indications for transplant listed above
• SAMD9 or SAMD9L disorders
• Criteria for Diagnosis: ** A pathogenic mutation(s) for SAMD9 or SAMD9L
• Indications for HCT:
• Severe neutropenia (ANC < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Congenital amegakaryocytic thrombocytopenia
• Criteria for Diagnosis:
• A pathogenic mutation(s) for congenital amegakaryocytic thrombocytopenia.
• For those patients tested but lacking a genetic mutation the patient must meet criteria below:
• Thrombocytopenia early in life, AND
• History of bone marrow demonstrating megakaryocyte hypoplasia
• Indications for HCT:
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Neutropenia defined as an ANC < 500/uL, OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Paroxysmal nocturnal hemoglobinuria
• Criteria for Diagnosis:
• Paroxysmal nocturnal hemoglobinuria (PNH) clone size in granulocytes >= 10%, AND
• Complement mediated intravascular hemolysis with an elevated LDH (above institutional upper limits of normal)
• Indications for HCT:
• PNH with thrombosis despite adequate medical management, OR
• PNH with intravascular hemolysis requiring transfusion support despite adequate medical management, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC. In addition, patients with PNH and cytopenias may be considered for the protocol eligibility following review by protocol 1904 ERC
• An undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified (excluding PNH) will be eligible for this clinical trial following approval by Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1904 ERC * A BMFD with a known genetic mutation but not listed above will be eligible for this clinical trial following approval by BMT CTN 1904 ERC
• Patient and/or legal guardian must sign informed consent prior to initiation of conditioning for BMT CTN 1904
• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence
• Note: The following patients MUST be reviewed by the BMT CTN 1904 ERC in order to determine if they are eligible for this trial:
• All patients with Shwachman-Diamond syndrome, Diamond Blackfan anemia, congenital sideroblastic anemia, and congenital amegakaryocytic thrombocytopenia who have had genetic testing and lack a genetic mutation
• All patients with an undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified, excluding PNH
• All patients with a BMFD and a known genetic mutation that is not listed above
• All patients with GATA2 mutation and associated marrow failure
• All patients with SAMD9 or SAMD9L disorders
• There may be circumstances where a treating physician will consider a transplant for a patient with a BMFD who does not meet all the criteria listed under "indications for HCT". In these situations, treating physicians may submit their patient to the BMT CTN 1904 ERC for review in order to determine if the patient is eligible for this clinical trial based on additional clinical or laboratory information
• Many patients with BMFD can have bone marrow evaluations that raise concern for possible myelodysplastic syndrome (MDS) including but not limited to dysplastic bone marrow evaluations or cytogenetic abnormalities. However, in patients BMFD these findings are not necessarily diagnostic or consistent with MDS. Therefore, given the complexities of diagnosing MDS in patients with BMFD, all patients with bone marrow evaluations concerning for possible MDS should be submitted to the ERC for review to confirm or exclude MDS. This is particularly important as we do not want to exclude potentially eligible patients due to an incorrect diagnosis of MDS
• HLA-MATCHED RELATED DONOR: HLA-matched sibling: Must be a minimum HLA-6/6 matched to the recipient at HLA-A, -B (serologic typing) and DRB1 (high-resolution typing)
• HLA-MATCHED RELATED DONOR: HLA-matched related (phenotypic match): Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing.
• HLA-MATCHED RELATED DONOR: If a genetic mutation is known for the patient, the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must be screened for the same genetic mutation if clinically appropriate and should be confirmed to not have the same genetic disease (this does not include patients with PNH). Consult the protocol team with questions
• HLA-MATCHED RELATED DONOR: If a patient has an undefined BMFD (a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified), the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must have an evaluation as directed by the treating physician to confirm that the donor does not have the same underlying disease. This will include a complete blood count (CBC) with differential and potentially a bone marrow evaluation or other studies as directed by the treating physician
• UNRELATED DONOR: Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing
• UNRELATED DONOR: Mismatched for a single HLA-class 1 allele (HLA-A, -B, or -C) by high-resolution typing; OR
• UNRELATED DONOR: Mismatched for a single HLA DQB1 allele or antigen by high-resolution typing * Note: donor patient (DP) matching per institutional practice
• DONOR SELECTION RECCOMENDATIONS: in the case where there are multiple donor options, donors should be selected based on the following priority numbered below:
• Unaffected fully HLA-matched sibling
• Unaffected fully phenotypically HLA-matched related donor
• Fully HLA-matched unrelated donor
• Unrelated donor with single allele or antigen level mismatch at DQB1
• Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C)
Exclusion Criteria:
• Patients with idiopathic aplastic anemia, Fanconi anemia, dyskeratosis congenita, and congenital neutropenia
• Patients with MDS as defined by the World Health Organization (WHO) or leukemia
• Prior allogeneic HCT
• Patient's weight =< 10.0 kg (actual body weight and adjusted body weight) at time of study enrollment
• Lansky (patients < 16 years of age) or Karnofsky (patients >= 16 years of age) performance < 70%
• Left ventricular ejection fraction < 50% by echocardiogram or multi-gated acquisition (MUGA) scan * For patients unable to obtain a left ventricular ejection fraction, left ventricular shortening fraction of < 26%
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) < 50%, forced expiratory volume (FEV)1 < 50% predicted, and forced vital capacity (FVC) < 50% predicted
• For patients unable to perform pulmonary function tests (PFTs) due to age or developmental delay: oxygen (O2) saturation < 92% on room air
• On supplemental oxygen
• Estimated creatinine clearance < 60 mL/minute/1.73m^2 (estimated per institutional practice)
• Dialysis dependent
• Conjugated bilirubin > 2 x ULN for age (upper limit of normal [ULN], unless attributable to Gilbert's syndrome)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x ULN for age, or
• Fulminant liver failure or cirrhosis
• Iron overload - This exclusion criterion only applies to patients who are considered at risk for hepatic or cardiac iron overload. Therefore, not all patients enrolled on this protocol will undergo formal hepatic or cardiac iron assessment
• For patients >= 18 years with a history of significant transfusions defined as >= 8 packed red blood cell transfusions per year for >= 1 year or have received >= 20 packed red blood cell transfusions (lifetime cumulative) will require formal hepatic and cardiac iron measurement. In addition, patients with a prior history of hepatic or cardiac iron overload will also require formal assessment for iron overload. Patients are excluded if:
• Hepatic iron content >= 8 mg Fe/g dry weight by liver magnetic resonance imaging (MRI) using a validated methodology (such as T2 * MRI or ferriscan) or liver biopsy per institutional practice
• Cardiac iron content < 25 msec by cardiac T2 * MRI
• For patients < 18 years old with a history of significant transfusions defined as >= 8 packed red blood cell transfusions per year for >= 1 year or have received >= 20 packed red blood cell transfusions (lifetime cumulative) will require formal hepatic iron measurement. In addition, patients with a prior history of liver iron overload will also require formal assessment for iron overload. Patients are excluded if:
• Hepatic iron content >= 8 mg Fe/g dry weight by liver MRI using a validated methodology (such as T2 * MRI or ferriscan) or liver biopsy per institutional practice
• Uncontrolled bacterial infection within 1 week of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Uncontrolled viral or fungal infection within 30 days of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Positive for human immunodeficiency virus (HIV)
• Presence of clinically significant anti-donor human leukocyte antigen (HLA)-antibodies per institutional practice
• Prior solid organ transplant
• Patients with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ
• Demonstrated lack of compliance with prior medical care as determined by referring physician
• Females who are pregnant or breast-feeding
• Known hypersensitivity to treosulfan or fludarabine
• Known life-threatening reaction (i.e. anaphylaxis) to Thymoglobulin that would prohibit use for the patient as this study requires use of the Thymoglobulin preparation of anti-thymocyte globulin (ATG)
Drug: Treosulfan, Drug: Fludarabine Phosphate, Drug: Tacrolimus, Drug: Methotrexate, Biological: Lapine T-Lymphocyte Immune Globulin, Procedure: Peripheral Blood Stem Cell Transplantation, Procedure: Allogeneic Bone Marrow Transplantation, Other: Quality-of-Life Assessment
Bone Marrow Failure Syndrome, Congenital Amegakaryocytic Thrombocytopenia, Congenital Pure Red Cell Aplasia, Hereditary Sideroblastic Anemia, Myeloid Neoplasms With Germline GATA2 Mutation, Paroxysmal Nocturnal Hemoglobinuria, Shwachman-Diamond Syndrome
Bone Marrow Failure Disorders, HSCT, Treosulfan, Unrelated donor, Matched donor, mismatched donor, transplant
A Study to Determine Frequency of DNA-repair Defects in Men With Metastatic Prostate Cancer (PREVALENCE)
Study Contact - Participate-In-This-Study@its.jnj.com
Paul, Asit, K.
NCT03871816
Inclusion Criteria:
• Diagnosis of metastatic (Stage IV) prostate cancer (PC), confirmed by either biopsy of a metastatic tumor site or history of localized disease supported by metastatic disease on imaging studies (that is [i.e.], clearly noted in hospital/clinical records)
• Signed Informed consent form (ICF)
• No condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example [e.g.], compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Willing to provide a saliva, blood, and/or archival tumor tissue sample for genomic analysis
• No prior poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) for the treatment of prostate cancer
• No prior DNA-repair gene defect test results from a Janssen sponsored interventional trial
Other: Saliva, Blood, or and/or Archival Tumor Tissue Collection and Analysis
Metastatic Prostate Cancer
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Gowda, Madhu, S
NCT01790152
HM20000463
Inclusion Criteria:
Study Strata I, II, and III are closed for further patient entry as of March 31, 2021. The study remains open for existing medical record submission of Stratum IV
* STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
* Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
* STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma \[P9404, high-risk DFCI 95-01\] or Hodgkin lymphoma \[P9425/P9426\])
* STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
* STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest \[also includes fields directed towards the neck, upper abdomen, or spine\], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
* STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's \[COG?s\] Statistics and Data Center \[SDC\] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (IRB) specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims; patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution)
* STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
* STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM III: OSTEOSARCOMA SURVIVORS
* Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
* Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
* Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
* \< 31 years of age at time of initial osteosarcoma diagnosis
* Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
* No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction \>= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction \>= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
* Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m\^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
* No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
* No exposure to DRZ at any point in time
* All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3
* Individuals diagnosed with cancer prior to age 21 years, who required treatment with chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after completing anti-cancer-therapy for at least 1 year
* Must have screening echocardiograms for heart function as part of cancer therapy and off-therapy evaluations available (Digital Imaging and Communications in Medicine \[DICOM\] format). Images from Video Home System (VHS) tapes and reports only (without images) are not suitable
* Cannot have a known history of congenital heart disease (patent foramen ovale remain eligible) or underlying genetic syndrome associated with abnormal cardiovascular development or health (e.g., down syndrome)
* Based on echocardiography, must have either left ventricular fractional shortening =\< 28.0% or ejection fraction =\< 50.0% on at least two occasions, with at least one of these measurements occurring after cancer therapy completion and be in the absence of sepsis or any uncontrolled infection
* If the fractional shortening or ejection fraction criteria is only met on one occasion, this must be after cancer therapy completion, be in the absence of sepsis or any uncontrolled infection, and the patient must have subsequently started on chronic medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme \[ACE\]-inhibitor, angiotensin receptor blocker) lasting at least 6 months
* For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Assessment of Therapy Complications, OTHER: Laboratory Biomarker Analysis, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma in Remission, Leukemia in Remission, Lymphoblastic Lymphoma, Osteosarcoma, Recurrent Leukemia, Recurrent Lymphoma, Recurrent Malignant Neoplasm
Safety, Tolerability and Effectiveness of ALVR105 in Kidney Transplant Recipients
Fenner, Shawn - shawn.fenner@vcuhealth.org
Gupta, Gaurav
NCT04605484
HM20020745
Inclusion Criteria:
• Patients who had a kidney transplant performed greater than or equal to 28 days prior to enrollment
• At least 1 identified, suitably matched Posoleucel (ALVR105) cell line for infusion is available. (If a matching Posoleucel line is not available, the following patient data will be collected: demographic data and human leukocyte antigen [HLA] type.)
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female patient is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• She is a woman of non-childbearing potential (WONCBP) as defined in the protocol
• She is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in the protocol during the study treatment period and for at least 90 days after the last dose of study treatment. The Investigator should evaluate the potential for contraceptive method failure.
Exclusion Criteria:
• Undergone allogeneic hematopoietic cell transplantation
• Evidence or history of graft versus host disease (GVHD) or cytokine release syndrome (CRS).
• Uncontrolled or progressive bacterial or fungal infections
• Known or presumed pneumonia
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Pregnant or lactating or planning to become pregnant.
• Weight <40 kg.
• Patients who received, or planned to receive abatacept or belatacept, within 3 months of screening
Biological: Posoleucel (formerly known as ALVR105) cells, Biological: Placebo (visually identical to Posoleucel),
drug: Viralym-m (alvr105)
BK Virus Nephropathy, BK Virus Infection, Infectious and Parasitic Diseases (001-139)
Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy (REVITALIZE 1)
Lynn Wilson - lwilson@fractyl.com
Sanyal, Arun, J
NCT04419779
HM20020776
Inclusion Criteria:
• Male, and non-pregnant, non-lactating females
• Age between 21 and 70 years (both inclusive)
• Subjects with T2D on stable dose (up to maximally approved doses) of metformin and up to 2 ADAs (including either GLP1 or DPP-4i and/or, TZD), requiring a minimum of 20 units up to a maximum of 60 units of basal insulin
• Glycosylated hemoglobin A1c (HbA1c) of 7.5-9.5% (both inclusive) confirmed at the end of at least 3 weeks stable run-in period
• FPG ≥180 to <270 mg/dL (measured after overnight 8-hour fasting and 24-36 hours after the last dose of glargine) at the end of at least 3 weeks stable run-in period
• Body Mass Index (BMI) ≥ 24 to ≤ 40 kg/m2
• Women of child-bearing potential (WOCBP) should have negative urine beta human chorionic gonadotropin (hCG) pregnancy test and must agree to use two of the established contraceptive methods throughout the study duration
• Able to sign an informed consent form and comply with study requirements.
Exclusion Criteria:
• Known case of absolute insulin deficiency as indicated by clinical assessment, and a fasting plasma C-peptide of <0.6 ng/ml
• Any drugs or concomitant medications (such as psychoactive drugs such as carbamazepine, phenobarbital, sympathomimetics (ephedrine etc.), corticosteroids, anabolic steroids, and male sex hormones such as testosterone, etc.) that can interfere with glucose metabolism
• Subjects who either are on SGLT2i, meglitinides, sulphonylurea (SUs), short or rapid acting insulin or any other class of ADA other than permitted baseline ADAs at the time of consent or who have a known or documented SGLT2i and/or metformin intolerance prior to the study
• Recurrent or severe urinary tract or genital mycotic infections or history of GU infection within 4 weeks prior to informed consent
• ALT >3 times upper limit normal values unless if associated with underlying NAFLD
• Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
• Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
• Ketosis-prone T2D
• History of non-healing diabetic ulcers or amputations
• History of more than 1 severe hypoglycemia episode or unawareness within past 6 months of screening
• In case of two or more glucose alert values of ≤70 mg/dL (3.9 mmol/L) unless a clear correctable precipitating factor can be identified/clinically significant hypoglycemia with self-monitored or laboratory plasma glucose level < 54 mg/dL (3.0 mmol/L / severe hypoglycemic episode requiring third party assistance occurring during run-in period
• Known intestinal autoimmune disease, as evidenced by either a positive anti-glutamic acid decarboxylase (GAD) test, including Celiac disease, or pre-existing symptoms of lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine
• Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone (TSH) value outside the normal range at screening)
• Known history of thyroid cancer or hyperthyroidism who have undergone treatment within past 12 months or inadequately controlled hyperthyroidism
• An uncontrolled endocrine condition such as multiple endocrine neoplasia etc. (except T2D)
• Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug-refractory esophageal reflux symptoms, active and uncontrolled Gastroesophageal Reflux Disease (GERD) (grade 3 esophagitis or greater)
• Known history of a structural or functional disorder of the stomach, including gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia or type II and higher paraoesophageal hernia) cancer or any other disorder of the stomach
• Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Billroth 2, Roux-en-Y gastric bypass, gastric sleeve or other similar procedures or conditions
• Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
• Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis; or hepatic decompensation/acute liver disease during the last 6 months; or alcoholic or autoimmune chronic hepatitis
• Symptomatic gallstones or symptomatic kidney stones, acute cholecystitis
• Clinically active systemic infection
• Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV), who are on potential immunosuppressants or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator
• History of active malignancy or partial remission from clinically significant malignancy within the past 5 years (except basal or squamous cell skin cancer or carcinoma in situ or those received curative treatment and in complete remission for 5 years or if subject confirmed as cancer free)
• Known active coagulopathy, or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
• Subjects with active helicobacter pylori infection (Subjects may be enrolled if they had history of h pylori infection and were successfully treated)
• Known cases of anemia, thalassemia or conditions that affect red blood cell (RBC) turnover such as recent blood transfusion within 90 days
• Use of anticoagulation therapy (such as warfarin, coumadin, novel oral anticoagulants [NOAC]) or anti-platelet agents (such as thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit
• Use of drugs known to affect GI motility (e.g., metoclopramide)
• History of moderate to severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 (estimated by Modification of Diet in Renal Disease [MDRD]) or end stage renal failure or on dialysis
• History of myocardial infarction, stroke, or major event requiring hospitalization within the last 3 months prior to screening
• History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
• Known case of severe peripheral vascular disease
• Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
• Clinically significant electrocardiogram (ECG) findings such as new clinically significant arrythmia or conduction disturbances that increases risk and requires intervention as determined by the investigator
• Subjects who are at risk for pancreatitis particularly those with a recent fasting triglycerides value of > 600 mg/dL value done within past 3 months
• Actively participating in a weight loss program and is currently not in the maintenance phase
• General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist (e.g., ASA score 4 or higher) or contraindications to upper GI Endoscopy
• History of any illicit alcohol or substance abuse
• Use of weight loss medication such as Meridia, Xenical, or over the counterweight loss medications or other prescribed medications used specifically for purpose of weight loss
• Use of Dietary supplements or herbal preparations that may have unknown effects on glycemic control, risk of bleeding
• Participating in another ongoing clinical trial of an investigational drug or device
• History of non-adherence to treatment in the previous 6 months, as determined by the investigator based on patient history, HbA1c value and/or drug accountability
• Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical trial participation
• Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
• Recovered from severe COVID-19 infection (requiring hospitalization) however still have persistent long COVID-19 symptoms (i.e., they have not recovered for several weeks or months since the start of symptoms that were suggestive of COVID-19, irrespective if they are tested or not).
Device: Duodenal Mucosal Resurfacing (DMR), Device: Duodenal Mucosal Resurfacing (Sham)
Type 2 Diabetes
Type 2 Diabetes, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Revita System, Duodenal Mucosal Resurfacing, Insulin-Dependent Diabetes Mellitus
Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy (REACH CDM X)
Howell, Jodie - jodie.howell@vcuhealth.org
Johnson, Nicholas, E
NCT05004129
HM20023901
Inclusion Criteria:
Subjects who do not enter this study directly from completing the AMO-02-MD-2-003 study (i.e. subjects who did not complete AMO-02-MD-2-003, subjects who completed AMO-02-MD-2-003 but did not directly rollover or subjects who are re-entering AMO-02-MD-2-004), will not be considered eligible for the study without meeting all of the criteria below:
• Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1.
• Diagnosis must be genetically confirmed
• Subjects must be male or female aged ≥6 years to ≤45 years at Screening
• Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1)
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or legally authorized representative (LAR) provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Subjects entering directly from completing the antecedent AMO-02-MD-2-003 study will not be considered eligible for the study without meeting all of the criteria below:
• Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or LAR provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Key
Exclusion Criteria:
• Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
• New or change in medications/therapies within 4 weeks prior to Eligibility/Baseline Visit
• Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir)
• Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
• Current enrollment in a clinical trial of an investigational drug or enrollment in a clinical trial of an investigational drug in the last 6 months other than the AMO-02- MD-2-003 study
• Existing or historical medical conditions or complications (eg. neurological, cardiovascular, renal, hepatic, gastrointestinal, endocrine or respiratory disease) that may impact the interpretability of the study results
• Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry
DRUG: Tideglusib
Congenital Myotonic Dystrophy
Tideglusib, AMO-02-MD-2-004, Congenital Myotonic Dystrophy, Myotonic Dystrophy, Dystrophia Myotonica, Myotonia Atrophica, Myotonia Dystrophica, Myotonic Dystrophy, Congenital, Steinert Disease, Steinert Myotonic Dystrophy, Steinert's Disease
TruGraf® Long-term Clinical Outcomes Study (TRULO)
Isioma Agboli, MD - isiomaagboli@eurofins-tgi.com
Moinuddin, Irfan
NCT04491552
HM20020284
Inclusion Criteria:
• Written informed consent and HIPAA authorization;
• At least 18 years of age;
• Recipient of a primary or subsequent deceased-donor or living-donor kidney transplant;
• At least 3-months post-transplant;
• Stable serum creatinine (per Principal Investigator);
• Treated with any immunosuppressive regimen, and;
• Selected by provider to undergo OmniGraf™ (TruGraf® and TRAC™) testing as part of post-transplant care; and
Exclusion Criteria:
• Recipient of a combined organ transplant with an extra-renal organ and/or islet cell transplant;
• Recipient of a previous non-renal solid organ and/or islet cell transplant;
• Known to be pregnant;
• Known to be infected with HIV;
• Known to have Active BK nephropathy;
• Known to have nephrotic proteinuria (Per Principal Investigator);
• Participation in other biomarker studies testing clinical utility.
Diagnostic Test: Patients monitored with TruGraf and TRAC testing
Kidney Transplant Rejection
Biomarkers, Subclinical Rejection
Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function (PROTECT IV)
Charles (Chuck) Simonton, MD FACC FSCAI - csimonton@abiomed.com
NCT04763200
Pending IRB#
Inclusion Criteria:
• Age ≥18 years and ≤90 years
• Clinical presentation and baseline left ventricular function are as follows: Either 2A or 2B must be present A. Subject has CCS or NSTEMI with an LVEF ≤40% NOTE: The LVEF must be quantitatively measured as ≤40% by echo within 30 days assuming no change in clinical condition. If multiple echos have been performed within 30-days, the most recent test must be used to qualify the patient. NOTE: Subject qualifies if the quantitative site read LVEF is ≤30%; if the quantitative site read is \>30% - ≤40% the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment (Core Lab will provide \<48-hour turnaround). Similarly, if the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment. OR B. Subject has STEMI ≥24 hours and \<30 days after symptom onset with an LVEF ≤30% NOTE: In patients qualifying with recent STEMI, the LVEF must be demonstrated to be ≤30% by quantitative echocardiography after the primary PCI procedure (if performed) and within 72-hours prior to the planned randomization. If primary PCI was not performed, the qualifying echocardiogram will be the one taken during the index hospitalization closest to the index procedure. If the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤30% before subject enrollment.
• Local heart team (interventional cardiologist and cardiac surgeon) has determined that PCI is indicated and is the most appropriate management for the patient
• Complex PCI will be performed: Either 4A or 4B must be met A. One of the following must be present: i. Triple vessel disease is present (visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89)\] is present in all 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) with PCI planned in ≥2 of these vessels in the proximal or mid LAD, proximal or mid-LCX or proximal, mid- or distal RCA \[i.e., not a branch vessel\]) OR ii. Left main distal bifurcation or trifurcation disease (visually-assessed DS ≥50% \[or DS ≥30% if non-invasive evidence of ischemia in both the anterior and posterolateral distributions or left main IVUS MLA ≤6.0 mm2 or FFR ≤0.80 or iFR ≤0.89\] is present) with planned intervention of the left main plus at least 2 branch vessels (i.e., the ostial LAD, ostial LCX or ostial ramus) OR iii. Left main equivalent disease with both ostial LAD and ostial LCX having visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89\] and requiring intervention in both branches OR iv. Intervention of the last remaining vessel (native coronary artery or bypass graft) OR B. Multivessel disease is present (visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive or invasive evidence of ischemia is present\] in ≥2 of the 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) and PCI is planned of at least 2 separate complex lesions in main vessels or branch vessels each having one or more of the following characteristics: i. Long lesion (≥28 mm visually assessed) requiring ≥30 mm stent length (single or multiple) ii. Severe angiographic calcification (see Protocol definition) or requiring atheroablation iii. Any left main morphology not in Criterion A requiring intervention (e.g., isolated ostial or mid-shaft left main lesion or distal left main bifurcation lesion with a planned single provisional stent technique) iv. Non-left main bifurcation lesion requiring intervention in both the main branch and side branch v. CTO (TIMI 0 Flow) vi. Giant thrombus (length ≥3x vessel diameter) vii. SVG (other than focal (\<5 mm) disease of the proximal or distal anastomosis or in-stent restenosis) NOTES:
• The multiple lesions can be in the same vessel if separated by ≥10 mm - however, each separate lesion has to have one or more of the above characteristics
• PCI may be performed on additional non-qualifying lesions (i.e., without 1 or more of the above high-risk characteristics) as long as there are at least two lesions also undergoing PCI with each having 1 or more of the above characteristics)
• There are 2 exceptions to the rule that each separate lesion must have one or more of the above characteristics (as in Inclusion Criterion 4B above): The subject may qualify if undergoing complex PCI of a single lesion that has 2 or more of the above complex characteristics (as in Inclusion Criterion 4B above) if also: i. There is a CTO of a proximal or mid-LAD, proximal or mid-LCX or proximal, mid- or distal RCA (i.e., not a branch vessel) that will not be treated OR ii. The subject qualifies with recent STEMI with an LVEF ≤30% and the complex PCI is planned in a non-infarct vessel (i.e., a complex PCI in the infarct vessel does not qualify)
• Subject or legal guardian (permitted at US sites only) agrees to randomization and to follow all study procedures and provides informed, written consent
Exclusion Criteria:
Subjects must not meet ANY of the following Exclusion Criteria to participate in the Trial:
• STEMI ≤24 hours from the onset of ischemic symptoms or at any time if mechanical complications of transmural infarction are present (e.g., VSD, papillary muscle rupture, etc.)
• Cardiogenic shock (SBP \<80 mmHg for ≥30 mins and not responsive to intravenous fluids or hemodynamic deterioration for any duration requiring pressors or mechanical circulatory support, including IABP)
• Subject is presently or recently intubated for the current admission (NOTE: recently intubated patients must be extubated for \>24 hours with full neurologic recovery)
• Cardiorespiratory arrest related to the current admission unless subject is extubated for \>24 hours with full neurologic recovery and hemodynamically stable
• Any contraindication or inability to Impella placement in both the left and right common femoral artery based on clinical or imaging findings, including iliofemoral artery diameter \<5 mm, tortuous vascular anatomy or severe bilateral peripheral vascular disease of the iliac or femoral arteries that can't be adequately treated (e.g., with intravascular lithotripsy) NOTES:
• Computed tomography (CT), magnetic resonance angiography (MRA) or contrast angiography to assess the aorta and iliofemoral vasculature to ensure Impella compatibility must be performed within 90 days prior to randomization. It is recommended that this evaluation be performed prior to the index procedure. Absent a qualifying pre-procedure imaging study, contrast angiography of the potential Impella access vessel(s) must be performed in the Cath Lab before the planned enrollment after which the subject may be randomized if he/she still qualifies. Of note, if pre-procedure imaging was performed and after this test but before randomization there was a worsening in PVD symptoms, repeat imaging must be performed prior to randomization.
• If iliofemoral peripheral vascular disease is present precluding Impella use that can be adequately treated with angioplasty, atherectomy or lithotripsy (without a stent), the subject can be enrolled if such treatment is undertaken and is successful and uncomplicated - randomization must not be performed until such successful and uncomplicated treatment
• Iliofemoral stents placed within 6 months of enrollment with planned vascular access through these vascular segments
• Vascular access for Impella is required in any location other than the left or right common femoral artery (i.e., axillary access, transcaval access, etc., for Impella access are not permitted)
• Known left ventricular thrombus
• Incessant ventricular arrhythmias that would likely preclude stable Impella positioning
• Severe aortic stenosis or severe aortic insufficiency
• Prior mechanical valve or self-expanding TAVR (NOTE: prior bioprosthetic surgical valve or balloon expandable TAVR implanted \>24 hours pre-procedure is acceptable)
• Prior CABG within three (3) months or successful prior PCI of at least one (1) attempted lesion within 12 months (including during the index hospitalization prior to randomization), that has not experienced stent thrombosis or restenosis during that 12-month period; the one (1) exception is that patients may be enrolled if a primary PCI for STEMI was performed during the index hospitalization without MCS and that was ≥24 hours and \<30 days prior to randomization. NOTE: Successful PCI for this exclusion criterion is defined as a visually-assessed angiographic DS ≤50% in at least one (1) attempted lesion.
• Prior placement of IABP, Impella or any other MCS device for any reason during the index admission, prior to randomization
• Known severe pulmonary hypertension (right ventricular systolic pressure (RVSP) on echo or pulmonary artery systolic pressure (PASP) on right heart catheterization) \>70 mm Hg unless active vasodilator therapy in the Cath Lab is able to reduce the pulmonary vascular resistance (PVR) to \<3 Wood Units or between 3 and 4.5 Wood Units with v-wave less than twice the mean of the pulmonary capillary wedge pressure
• Symptoms or signs of severe RV dysfunction, such as anasarca (NOTE: Leg edema alone does not necessarily indicate severe RV dysfunction if the investigator believes it is due to LV dysfunction)
• Severe tricuspid insufficiency
• Platelet count \<75,000 cells/mm3, bleeding diathesis or active bleeding, coagulopathy or unwilling to receive blood transfusions
• On dialysis
• Prior stroke with any permanent neurologic deficit within the previous three (3) months, or any prior intracranial hemorrhage or any prior subdural hematoma or known intracranial pathology pre-disposing to intracranial bleeding, such as an arteriovenous malformation or mass
• Taking a chronic oral anticoagulant that cannot be safely discontinued for at least 72-hours before and 72-hours after the index procedure (if a vitamin K antagonist) or that cannot be safely discontinued for at least 48 hours before and 48 hours after the index procedure (for a direct acting oral anticoagulant)
• Plan for any surgery within 6 months necessitating discontinuing antiplatelet agents
• Pregnant or child-bearing potential unless negative pregnancy test within 1 week
• Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device that has not reached its primary endpoint
• Any medical or psychiatric condition such as dementia, alcoholism or substance abuse which may preclude informed consent or interfere with any of the study procedures, including follow-up visits
• Any non-cardiac condition with life expectancy \<3 years (e.g., cirrhosis, oxygen or oral steroid dependent COPD, cancer not in remission, etc.)
• Subject is currently hospitalized for definite or suspected COVID-19
• Subject has previously been symptomatic with or hospitalized for COVID-19 unless he/she has been discharged (if hospitalized) and asymptomatic for ≥4 weeks and has returned to his/her prior baseline (pre-COVID) clinical condition
• Subject is asymptomatic (never ill) and COVID-19 PCR/antigen test is positive within the prior four (4) weeks unless a) subject remains asymptomatic for ≥2 weeks after the last positive test or b) the positive test occurred within six (6) months after the subject received a COVID vaccine
• Subject belongs to a vulnerable population (defined as individuals with mental disability, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent; vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention)
DEVICE: Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®, DEVICE: IABP Intra-aortic balloon pump
Left Ventricular Dysfunction, Coronary Artery Disease
Non-ST Elevated Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Myocardial Ischemia, Myocardial Infarction, Anterior Wall Myocardial Infarction, Inferior Wall Myocardial Infarction
Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery (ASTER)
Katie Oldmixon, RN - coldmixon@mgh.harvard.edu
Fowler, Alpha, A
NCT04291508
HM20023257
Inclusion Criteria:
• Age ≥ 18 years
• Sepsis defined as:
• Clinical evidence of a known or suspected infection and orders written to administer antibiotics AND
• Hypotension as defined by the need for any vasopressor (and 1 liter of fluid already administered intravenously for resuscitation) OR respiratory failure defined by mechanical ventilation, BIPAP or CPAP at any level, or greater than or equal to 6 liters/minute of supplemental oxygen (criterion b must be met at time of enrollment)
• Admitted to a study site ICU (or intent for the patient to be admitted to a study site ICU) within 36 hours of presentation to the ED or admitted to the study site ICU within 36 hours of presentation to any acute care hospital
Exclusion Criteria:
• No consent/inability to obtain consent from the participant or a legally authorized representative
• Patient unable to be randomized within 36 hours of presentation to the ED or within 36 hours of presentation to any acute care hospital
• Diagnosis of cirrhosis by medical chart review
• Liver transplant recipient
• AST or ALT greater than five times upper limit of normal
• Diagnosis of ongoing chronic alcohol use disorder/abuse by chart review; if medical record unclear, use Appendix F
• Clinical diagnosis of diabetic ketoacidosis or other condition such as profound hypoglycemia that requires hourly blood glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Hypersensitivity to Acetaminophen or Vitamin C
• Patient, surrogate or physician not committed to full support (Exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
• Home assisted ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing
• Chronic dialysis
• Current active kidney stone (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Multiple (>1) episodes of prior kidney stones, known history of oxalate kidney stones, or history of oxalate nephropathy. (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Kidney transplant recipient (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Use of home oxygen >3L/minute via nasal cannula for chronic cardiopulmonary disease
• Moribund patient not expected to survive 24 hours
• Underlying malignancy or other condition with estimated life expectancy of less than 1 month
• Pregnant woman, woman of childbearing potential without a documented negative urine or serum pregnancy test during the current hospitalization, or woman who is breast feeding
• Prisoner
• Treating team unwilling to enroll because of intended use of Acetaminophen or Vitamin C
• Treating team unwilling to use plasma (as opposed to point of care testing) for glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial).
Drug: Intravenous Acetaminophen (room temperature), Drug: Intravenous Vitamin C (refrigerated), Drug: 5% Dextrose (room temperature), Drug: 5% Dextrose refrigerated
Acute Respiratory Distress Syndrome, Critical Illness, Respiratory Failure, Sepsis
ARDS, Acetaminophen, Vitamin C, Sepsis
Trifecta-Kidney cfDNA-MMDx Study
Konrad S Famulski, PhD - konrad@ualberta.ca
NCT04239703
Inclusion Criteria:
* All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.
Exclusion Criteria:
* Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients. DIAGNOSTIC_TEST: MMDx, DIAGNOSTIC_TEST: Prospera, DIAGNOSTIC_TEST: HLA antibody
Kidney Transplant Rejection
donor derived cell-free DNA, blood, kidney biopsy
Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial (INNOVATE)
Loney, Shenise - loneys2@vcu.edu
Urdaneta, Alfredo, I
NCT04134260
HM20021914
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
* Any T-stage is eligible (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed\])
* Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA \< 0.20 ng/mL at time of registration, PET scan is recommended but not required
* Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
* History/physical examination within 90 days prior to registration
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
* Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA \> 0 ng/mL at least 30 days after prostatectomy
* Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =\< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =\< 180 days and stopped prior to registration)
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
* Serum potassium \>= 3.5 mmol/L within 90 days prior to registration
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 90 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 90 days prior to registration)
* Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for \< 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, \[FACBC, Axumin\], F-18 PSMA PET \[Pylarify\], flotufolastat F-18 PSMA PET scan \[Posluma\], Gallium-68 PSMA PET scan or C-11 choline PET)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Androgen deprivation therapy (ADT) prior to radical prostatectomy
* Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =\< 180 days and stopped prior to registration, which is allowed
* Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:
* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
* Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
* New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.)
* History of any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:
* Known gastrointestinal disorder affecting absorption of oral medications
* Active uncontrolled infection
* Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
* Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
* Baseline moderate and severe hepatic impairment (Child-Pugh Class B \& C)
* Inability to swallow oral pills
* Any current condition that in the opinion of the investigator, would preclude participation in this study
* Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
* Patients with inflammatory bowel disease DRUG: Apalutamide, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Hormone Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy
Prostate Adenocarcinoma, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8
Prostate Cancer, Apalutamide, Abiraterone Acetate
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF (Rebalance-HF)
Judit Adorjan - j.adorjan@axontherapies.com
Shah, Keyur, B
NCT04592445
HM20022228
Inclusion Criteria
• Chronic heart failure, defined as:
• Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
• NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
• At least one of the following: i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
• Age ≥40 years.
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
• MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
• Cardiac resynchronization therapy initiated within 3 months prior to screening.
• Advanced heart failure defined as one or more of the following:
• ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
• Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
• Subject is on the cardiac transplant waiting list.
• Presence of or prior history of mechanical circulatory support for HF.
• Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio \>2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% assessed by the screening echocardiogram.
• Body mass index (BMI) \>45 kg/m2.
• 6-minute walk test distance \<100 meters OR \>450 meters.
• Admission for HF within the 30 days prior to planned index procedure.
• Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of \>20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
• Orthostatic pulse pressure change from supine to standing decrease of \>10mmHg in the absence of a HR increase \>15bpm
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• Systolic BP \<100 mmHg or \>170 mmHg despite appropriate medical management.
• Baseline screening ECG resting HR \>100 beats per minute or ventricular tachycardia.
• Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
• Left ventricular EF \<40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• Presence of significant valve disease defined by the site cardiologist as:
• Greater than mild mitral valve stenosis.
• Greater than moderate mitral valve regurgitation.
• Greater than moderate-to-severe tricuspid valve regurgitation.
• Greater than moderate aortic valve stenosis or regurgitation.
• Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
• History of clinically significant liver cirrhosis.
• Prior weight loss surgery
• Dialysis dependent; or estimated GFR \<25 ml/min/1.73 m2 by CKD-EPI creatinine equation.
• Arterial oxygen saturation \<90% on room air.
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
• Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
• Life expectancy \<12 months for non-cardiovascular reasons.
• Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
• Females who are pregnant or lactating or planning to become pregnant during the next year.
• Any of the following measured by screening right heart catheterization:
• Mean right atrial pressure (RAP) \>20 mmHg at rest
• Cardiac index \<2.0 L/min/m2 at rest
• Pulmonary vascular resistance (PVR) \>4 Wood units Exclusion Criteria Assessed During the index procedure:
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.
• Chronic heart failure, defined as:
• Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
• NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
• At least one of the following: i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
• Age ≥40 years.
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
Exclusion Criteria:
• MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
• Cardiac resynchronization therapy initiated within 3 months prior to screening.
• Advanced heart failure defined as one or more of the following:
• ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
• Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
• Subject is on the cardiac transplant waiting list.
• Presence of or prior history of mechanical circulatory support for HF.
• Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio \>2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% assessed by the screening echocardiogram.
• Body mass index (BMI) \>45 kg/m2.
• 6-minute walk test distance \<100 meters OR \>450 meters.
• Admission for HF within the 30 days prior to planned index procedure.
• Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of \>20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
• Orthostatic pulse pressure change from supine to standing decrease of \>10mmHg in the absence of a HR increase \>15bpm
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• Systolic BP \<100 mmHg or \>170 mmHg despite appropriate medical management.
• Baseline screening ECG resting HR \>100 beats per minute or ventricular tachycardia.
• Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
• Left ventricular EF \<40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• Presence of significant valve disease defined by the site cardiologist as:
• Greater than mild mitral valve stenosis.
• Greater than moderate mitral valve regurgitation.
• Greater than moderate-to-severe tricuspid valve regurgitation.
• Greater than moderate aortic valve stenosis or regurgitation.
• Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
• History of clinically significant liver cirrhosis.
• Prior weight loss surgery
• Dialysis dependent; or estimated GFR \<25 ml/min/1.73 m2 by CKD-EPI creatinine equation.
• Arterial oxygen saturation \<90% on room air.
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
• Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
• Life expectancy \<12 months for non-cardiovascular reasons.
• Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
• Females who are pregnant or lactating or planning to become pregnant during the next year.
• Any of the following measured by screening right heart catheterization:
• Mean right atrial pressure (RAP) \>20 mmHg at rest
• Cardiac index \<2.0 L/min/m2 at rest
• Pulmonary vascular resistance (PVR) \>4 Wood units Exclusion Criteria Assessed During the index procedure:
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.
DEVICE: Greater Splanchnic Nerve Ablation, DEVICE: Sham Control
Heart Failure With Preserved Ejection Fraction (HFpEF
Heart Failure with Preserved Ejection Fraction (HFpEF), HFpEF, Greater Splanchnic Nerve, GSN
Therapeutic Hepatitis C Virus Vaccine
Smith, Paula - paula.smith@vcuhealth.org
Sterling, Richard, K
NCT04318379
HM20021916
Inclusion Criteria:
• Documentation of chronic hepatitis C infection based on serum positivity for HCV RNA for at least 6 months interval. HCV genotype will be recorded. All genotypes will be eligible.
• Patients who are not under DAA treatment.
• Liver fibrosis (by Metavir stage F1 or F0) within one year of the screening visit, documenting extent of liver disease consistent with chronic hepatitis C with evidence of inflammation and/or fibrosis. Fibrosis scaling is based on an ultrasound based elastography (FibroScan, Echosen, Paris France) with cutoff of 7.5 kPa or liver biopsy.
• Screening laboratory values within institutional normal range, with the exception of liver enzymes ? 3 ULN and bilirubin <1.5 ULN, or judged to be not clinically significant by clinical investigator.
• Ability and willingness of subject to give written informed consent.
• Negative pregnancy test on the day prior to each vaccination.
• Willingness to use adequate contraception by study participants. Subjects must agree not to participate in a conception process (e.g., active attempts to become pregnant or to impregnate, sperm donation, or in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, subjects must use a form of contraception as listed below while on study vaccine and for 60 days after stopping study vaccine. Women without reproductive potential (i.e., have reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) or women whose male partner has undergone successful vasectomy with documented azoospermia or has documented azoospermia for any other reason, are eligible without requiring the use of contraception.
Exclusion Criteria:
• History of decompensated liver disease, including but not restricted to, portal hypertension as manifested by a known history of gastroesophageal varices, variceal bleeding, ascites or encephalopathy, histopathologic or clinical evidence of cirrhosis, hepatocellular carcinoma, or renal impairment consistent with hepatorenal syndrome; history of significant other non-HCV chronic liver disease, i.e. alcoholic hepatitis, autoimmune hepatitis.
• History of hematologic disease (e.g., cryoglobulinemia, lymphoma), renal disease, dermatologic disease (e.g., lichen planus, porphyria cutanea tarda).
• Seropositive for hepatitis B surface antigen (HBsAg) or HIV-1 antibody.
• Autoimmune diseases or clinically serious cardiac, pulmonary, gastrointestinal, hepatic, renal or neurologic disease, which in the opinion of the investigator will compromise ability to participate in the study.
• Previous receipt of any HCV experimental vaccine.
• Pregnancy and breast-feeding.
• Prior or current systemic cancer chemotherapy.
• Investigational agents and immunomodulators (cyclosporine, hematological growth factors, systemic corticosteroids, interleukins or interferons) within 90 days prior to study entry. NOTE: Subjects may not be on antiretroviral agents not yet approved by the FDA as part of a clinical trial or expanded access program.
• Anaphylaxis or allergy to vaccine components.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Any other serious diseases other than HCV infection including current or recent (within 5 years) cancers.
• Liver fibrosis with Metavir stage F2 or above.
• Subjects with diabetes mellitus, who are at higher risk for more rapid progression of fibrosis.
• Subjects who are immunocompromised or immunosuppressed due to disease or medications.
• Subjects with any laboratory abnormalities Grade 3 or greater.
• Women who are lactating.
Biological: HCVax,
drug: Hcvax?
Chronic Hepatitis C Infection, Infectious and Parasitic Diseases (001-139)
Therapeutic HCV vaccine, HCV
Preventing Firearm Violence in Youth: A Hospital-based Prevention Strategy
Nicholas Thomson - Nicholas.Thomson@vcuhealth.org
Thomson, Nicholas
NCT05078164
HM20022975
Inclusion Criteria:
• Youth are aged 10-17 years and their adult caregivers are aged 18 years and older
• Receiving treatment in the hospital for a violence-related injury (e.g., gunshot wound) or referred to BTG/IVPP services
• English speaking
• Eligible for BTG services (which includes living within the BTG catchment area for the hospital; Richmond City and neighboring counties)
Exclusion Criteria:
• Youth are \< 10 years old
• Youth are \> 18 years old
• Prisoners
BEHAVIORAL: Bridging the Gap (BTG)
Violence in Adolescence
A Study to Learn About How Well Riociguat Works, How Safe it is and How it is Used Under Real World Conditions in Patients in the United States Who Are Receiving Riociguat for High Blood Pressure in the Arteries That Carry Blood From the Heart to the Lungs (Pulmonary Arterial Hypertension, PAH) (ROAR)
Bayer Clinical Trials Contact - clinical-trials-contact@bayer.com
Grinnan, Daniel, C
NCT04813926
HM20022707
Inclusion Criteria:
• Patients aged ≥18 years at the time of riociguat treatment initiation
• Diagnosis of PAH per National Institute for Health and Care Excellence (NICE) 2018 classification
• Decision to initiate treatment with riociguat as per investigator's routine treatment practice made prior to enrollment in the study
• Initiation of riociguat, as per the FDA-approved US label:
• At enrollment OR
• ≤90 days prior to enrollment, with a documented titration regimen (defined as all documented dose changes including, but not limited to: starting dose and dates and highest tolerated dose and dates)
• Signed informed consent
Exclusion Criteria:
• Previously treated with and discontinued use of riociguat for any reason prior to study enrollment (discontinuation defined as an interruption of therapy ≥30 days)
• Participating in any of the following:
• Blinded clinical trial
• Clinical trial involving an unapproved drug
• Investigational program with interventions outside of routine clinical practice
• Life expectancy <12 months
• Contraindicated to receive riociguat per the FDA approved US label
• Use of nitrates or NO donors in any form
• Use of PDE5 inhibitors
• PH associated with idiopathic interstitial pneumonias
• Unable or unwilling to provide informed consent
Drug: Riociguat (Adempas, BAY63-2521)
Pulmonary Arterial Hypertension
A Pilot Study to Examine the Impact of a Therapy Dog Intervention on Loneliness and Related Health Outcomes in Vulnerable Populations
Nancy R. Gee, PhD - Nancy.Gee@vcuhealth.org
Gee, Nancy
NCT05089201
HM20021567
Inclusion Criteria:
• 18 years of age or older
• Projected to be admitted to the hospital for the upcoming four days
• Speak English
• Able to provide consent.
Exclusion Criteria:
• Fear of, or allergy to, dogs
• Documented contact precautions
• Cognitive impairment that prevents consent or completion of measures.
Behavioral: Animal-assisted interaction, Behavioral: Conversational control
Loneliness, Depression, Anxiety, Quality of Life
Phase 3 Study of MRTX849 +Cetuximab vs Chemo in Patients W/ Advanced Colorectal Cancer w/ KRAS G12C
Donovan, Carrie - cdonovan2@vcu.edu
Matin, Khalid
NCT04793958
HM20022574
Inclusion Criteria:
• Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue.
• Prior receipt of 1st line treatment in advanced CRC with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan, and radiographically documented progression of disease on or after treatment.
Exclusion Criteria:
• Prior treatment with a therapy targeting KRAS G12C mutation (e.g., AMG 510).
• Prior treatment with an anti-EGFR antibody (e.g., cetuximab or panitumumab).
• Active brain metastasis
Drug: MRTX849, Biological: Cetuximab, Drug: mFOLFOX6 Regimen, Drug: FOLFIRI Regimen,
drug: Mrtx849,
drug: Leucovorin,
drug: Folinic acid,
drug: Cetuximab,
drug: 5-fluorouracil
Advanced Colorectal Cancer, Metastatic Colorectal Cancer, Rectum, Colon
Colorectal Cancer, Colorectal Cancer Trial, Colorectal Carcinoma, Rectal Cancer, Colon Cancer, KRAS, KRAS G12C, RAS, Colorectal Adenocarcinoma
Novel Experimental COVID-19 Therapies Affecting Host Response (NECTAR)
Sheri L. Dixon, B.S.N., R.N. - sheri.dixon@vumc.org
de Wit, Marjolein
NCT04924660
HM20022625
Inclusion criteria
• Hospitalized for COVID-19
• ≥18 years of age
• SARS-CoV-2 infection, documented by:
• a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
• documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
• Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
• Symptoms or signs of acute COVID-19, defined as one or more of the following:
• cough
• reported or documented body temperature of 100.4 degrees Fahrenheit or greater
• shortness of breath
• chest pain
• infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) Exclusion criteria
• Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
• Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
• Pregnancy
• Breastfeeding
• Prisoners
• End-stage renal disease (ESRD) on dialysis
• Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life.
• The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
• Known allergy/hypersensitivity to IMP or its excipients The following exclusion criteria differ from the master protocol criteria: TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual):
• Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual):
• Participants on ARBs will be excluded from this study arm.
• Patient unable to participate or declines participation in the TRV027 arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days Fostamatinib specific exclusion criteria: The following exclusion criteria differ from the master protocol criteria:
• Randomized in another trial evaluating fostamatinib in the prior 30 days Study arm exclusion criteria measured within 24 hours prior to randomization:
• AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
• SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
• ANC < 1000/mL
• Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
• Patient unable to participate or declines participation in the fostamatinib arm.
• Hospitalized for COVID-19
• ≥18 years of age
• SARS-CoV-2 infection, documented by:
• a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
• documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
• Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
• Symptoms or signs of acute COVID-19, defined as one or more of the following:
• cough
• reported or documented body temperature of 100.4 degrees Fahrenheit or greater
• shortness of breath
• chest pain
• infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) Exclusion criteria
• Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
• Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
• Pregnancy
• Breastfeeding
• Prisoners
• End-stage renal disease (ESRD) on dialysis
• Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life.
• The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
• Known allergy/hypersensitivity to IMP or its excipients The following exclusion criteria differ from the master protocol criteria: TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual):
• Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual):
• Participants on ARBs will be excluded from this study arm.
• Patient unable to participate or declines participation in the TRV027 arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days Fostamatinib specific exclusion criteria: The following exclusion criteria differ from the master protocol criteria:
• Randomized in another trial evaluating fostamatinib in the prior 30 days Study arm exclusion criteria measured within 24 hours prior to randomization:
• AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
• SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
• ANC < 1000/mL
• Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
• Patient unable to participate or declines participation in the fostamatinib arm.
Drug: TXA127, Drug: TRV027, Drug: Placebo, Drug: Fostamatinib
COVID-19, SARS-CoV-2 Infection, Coronavirus Infection
COVID-19 drug treatment, RAAS
CONTIGO - A Narrative Intervention to Enhance Genetic Counseling and Testing
Alejandra Hurtado de Mendoza, Ph.D - ahd28@georgetown.edu
NCT05130606
Inclusion Criteria:
Aim 1 and 2.
* Self-identify as a Latina woman
* Be 18 years old or older
* Be able to provide informed consent
* Be fluent in Spanish
* Meet NCCN criteria to be considered for genetic cancer risk assessment for HBOC, whether by a personal history of cancer or family history of cancer
* No previous participation in genetic counseling or testing for hereditary breast and ovarian cancer risk
* No other family members are participating in this study
* Have not participated in any previous studies involving interventions about HBOC or GCT
Aim 3.
* Be 18 years old or older
* Be fluent in English or Spanish
* Have a role in the partner community clinic as either a) full-time or part-time employee b) intern c) volunteer
Exclusion Criteria:
\- BEHAVIORAL: Culturally Targeted Narrative Video: "Is My Cancer Hereditary? Rosa Visits a Genetic Counselor.", BEHAVIORAL: FORCE Fact Sheet
Hereditary Breast and Ovarian Cancer
Breast cancer, Ovarian cancer, Hereditary cancer, Latinas