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A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Reference Study ID Number: NP30179 https://forpatients.roche.com/ - global-roche-genentech-trials@gene.com
Yazbeck, Victor, Y
Phase 1/Phase 2
NCT03075696
Inclusion Criteria:
• Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (CD)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [ASCT])
• Measurable disease, defined as at lease one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measureable extranodal lesion, defined as > 1.0 cm in its longest dimension
• Able to provide a fresh biopsy from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of >/=12 weeks
• AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to ( • Adequate liver, hematological and renal function
• Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic Hepatitis B virus (HBV) infection
• Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
• Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test
Exclusion Criteria:
• Inability to comply with protocol mandated hospitalizations and restrictions
• Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
• Participants with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
• Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
• Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA4], anti-programmed death 1 [anti-PD1] and anti-programmed death ligand 1 [anti-PDL1]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on Cycle 1 Day -7
• History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents
• Documented refractoriness to an obinutuzumab-containing regimen
• Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including chimeric antigen receptor therapy (CAR-T) within 4 weeks prior to obinutuzumab infusion
• Prior solid organ transplantation
• Prior allogeneic SCT
• Autologous SCT within 100 days prior to obinutuzumab infusion
• Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Current or past history of central nervous system (CNS) lymphoma
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a past history of stroke that have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits are allowed.
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
• Participants with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence)
• Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
• Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion or anticipation that such a live attenuated vaccine will be required during the study
• Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to obinutuzumab infusion. Treatment with corticosteroid • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus, erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Participants with a remote history of, or well controlled autoimmune disease, may be eligible to enroll after consultation with the Medical Monitor
• In Part III DLBCL dexamethasone cohort, patients with a history of hypersensitivity to dexamethasone or systemic corticosteroids will be excluded
Drug: Glofitamab, Drug: Obinutuzumab, Drug: Tocilizumab
Non-Hodgkin's Lymphoma
Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (BEAT-MS)
Vences, Karina - venceskm@vcu.edu
Oh, Unsong
PHASE3
NCT04047628
HM20017222
Inclusion Criteria:
• Age 18 to 55 years, inclusive, at the time of the screening Visit -2.
• Diagnosis of MS according to the 2017 McDonald Criteria139.
• EDSS ≤ 6.0 at the time of randomization (Day 0).
• T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for dissemination in space139. A detailed MRI report or MRI images must be available for review by the site neurology investigator.
• Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria described below:
• At least one episode of disease activity must occur following ≥ 1 month of treatment with one of the following: (i) an oral DMT approved by the FDA for the treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include: dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide, cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab, ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and
• At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
• At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item c.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee (see Section 3.5), and ii. MRI evidence of disease activity must include ≥ 1 unique active lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following: 1\. A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a reference scan obtained not more than 36 months prior to the screening visit (Visit -2). 6\. Candidacy for treatment with at least one of the following high efficacy BAT DMTs: cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab. Candidacy for treatment for each BAT DMT is defined as meeting all of the following:
• No prior disease activity episode, as defined in Inclusion Criterion #5, with the candidate BAT DMT, and
• No contraindication to the candidate BAT DMT, and
• No treatment with the candidate BAT DMT in the 12 months prior to screening. 7\. Completion of COVID-19 vaccination series, according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations, ≥ 14 days prior to randomization (Day 0). 8\. Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0). 9\. Insurance approval for MS treatment with at least one candidate BAT DMT (see Inclusion Criterion #6). 10\. Ability to comply with study procedures and provide informed consent, in the opinion of the investigator. 11\. Females of childbearing potential (defined in Section 5.4.3.1) and males with female partners of childbearing potential are required to adhere to the contraception provisions of Section 5.4.3.1. 12\. For participants who use medicinal or recreational marijuana, willingness to substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6).
Exclusion Criteria:
• Diagnosis of primary progressive MS according to the 2017 McDonald criteria.
• History of neuromyelitis optica spectrum disorder or MOG antibody disease.
• Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of COVID-19 are not considered investigational.
• Either of the following within one month prior to randomization (Day 0):
• Onset of acute MS relapse, or
• Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
• Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day 0).
• Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML).
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis.
• History of sickle cell anemia or other hemoglobinopathy.
• Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Presence or history of mild to severe cirrhosis.
• Hepatic disease with the presence of either of the following:
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
• Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0).
• Evidence of HIV infection.
• Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test.
• Active viral, bacterial, endoparasitic, or opportunistic infections.
• Active invasive fungal infection.
• Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist.
• Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0).
• Presence or history of clinically significant cardiac disease including: a. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions. b. Coronary artery disease with a documented diagnosis of either: i. Chronic exertional angina, or ii. Signs or symptoms of congestive heart failure. c. Evidence of heart valve disease, including any of the following: i. Moderate to severe valve stenosis or insufficiency, or ii. Symptomatic mitral valve prolapse, or iii. Presence of prosthetic mitral or aortic valve.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2, according to the CKD-EPI formula144.
• Forced expiratory volume in one second (FEV1) \< 70% predicted (no bronchodilator).
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) \< 70% predicted.
• Poorly controlled diabetes mellitus, defined as HbA1c \> 8%.
• History of malignancy, except adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. Malignancies for which the participant is judged to be cured will be considered on an individual basis by the study adjudication committee (see Section 3.5).
• Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following: systemic lupus erythematous, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, polymyositis, dermatomyositis, mixed connective tissue disease, polymyalgia rheumatica, polychondritis, sarcoidosis, vasculitis syndromes, or unspecified collagen vascular disease.
• Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer.
• Prior history of AHSCT.
• Prior history of solid organ transplantation.
• Positive pregnancy test or breastfeeding.
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent.
• History of hypersensitivity to rabbit or Escherichia coli-derived proteins.
• Any metallic material or electronic device in the body, or other condition that precludes the participant from undergoing MRI with gadolinium administration, as determined by the site radiologist.
• Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage.
• Presence or history of other neurological disorders, including but not limited to CNS or spinal cord tumor; metabolic or infectious cause of myelopathy; genetically-inherited progressive CNS disorder; CNS sarcoidosis; or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
• Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality.
• Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, BIOLOGICAL: Best Available Therapy (BAT)
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT
Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease
uniQure - medinfo@uniqure.com
Barrett, Matthew, James
PHASE1
NCT04120493
HM20015806
Inclusion Criteria:
* Able and willing to provide written informed consent prior to the study and study-related procedure
* Participants 25 to 65 years of age of both sexes
* Cohorts 1, 2, \& 3: Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic confidence level (DCL) of 4 OR a DCL of 3 if the subject either meets the definition of multidimensional manifest HD (UHDRS question 80) or has cognitive symptoms
* Cohort 3: Early manifest HD as defined by a UHDRS TFC score of ≥ 11 and EITHER a DCL of 4 or a DCL of 3 with either a positive "Yes" response to UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder (Movement Disorder Society Task Force criteria).
* HTT gene expansion testing with the presence of ≥40 CAG repeats
* Striatal MRI volume requirements per hemisphere:
* Cohorts 1, 2, \& 3: Putamen ≥2.5 cm\^3 (per side); Caudate ≥2.0 cm\^3 (per side)
* Cohort 4: Putamen \<2.5 cm\^3 (on either side); Caudate \<2.0 cm\^3 (on either side)
* All HD concomitant medications (addressing motor, behavioral, and cognitive symptoms) must be stable for 3 months prior to Screening with no change in clinical symptoms requiring change in medication prior to anticipated administration procedure
* Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol
* All female participants of childbearing potential (FOCP) must have a negative serum pregnancy test at Screening, (and Visit 1A, as appropriate), a negative pregnancy urine dipstick at Baseline, and not be breastfeeding. All FOCPs and sexually mature males must be compliant with a highly effective birth control method.
Exclusion Criteria:
* Evidence of suicide risk
* Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
* Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or anytime over the duration of this study.
* Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter
* Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASOs), cell transplantation or any other experimental brain surgery.
* Any contraindication to 3.0 Tesla MRI as per local guidelines
* Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder
* Any contraindication to lumbar puncture as per local guidelines
* Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
* Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
* Current or recurrent disease, (including pre-existing cardiovascular or pulmonary conditions) infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a participant's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule
* Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients
* Any known allergy to gadoteridol (ProHance)
* Screening laboratory values (as measured by the central laboratory): a. Alanine aminotransferase (ALT) \>2 × upper limit of normal (ULN) b. Aspartate aminotransferase (AST) \>2 × ULN c. Total bilirubin \>2 × ULN d. Alkaline phosphatase (ALP) \>2 × ULN e. Creatinine \>1.5 × ULN f. Platelet count \<100,000/mm3g.Prothrombin time (PT) \>1.2 × ULN h. Partial thromboplastin time (PTT) \>1.2 × ULN
* Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol.
* Any participant with an active infection (e.g., coronavirus disease 2019 \[COVID-19\]) at Screening or at the time of treatment that requires medical intervention. Participants may rescreen, or if screened eligible and an open surgical slot is available, may receive treatment after recovery.
* Cohort 4 ONLY: Inability to establish a safe trajectory to administer AMT-130 to the target structures, as assessed by neuroimaging. GENETIC: intra-striatal rAAV5-miHTT, OTHER: Imitation (sham) surgery
Huntington's Disease
Gene therapy, AAV (adeno-associated virus), serotype 5 AAV (adeno-associated virus), serotype 5, Viral vector, miHTT, muHTT, Huntington's Disease (HD)
Diagnostic and Therapeutic Applications in Microarrays in Organ Transplantation
Philip F Halloran, MD PhD - phallora@ualberta.ca
NCT01299168
Inclusion Criteria:
* All kidney transplant recipients ≥18yrs of age undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enrol in the study.
Exclusion Criteria:
* Patients will be excluded from the study if they decline participation or are unable to give informed consent. Validation Study of Molecular Diagnostic System, Development of Reporting System for Molecular Diagnosis, Incorporate Molecular Diagnosis Into Diagnostic Standards
global gene expression, molecular diagnostic classifiers
A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer
Reference Study ID Number: YO40482 https://forpatients.roche.com/ - global-roche-genentech-trials@gene.com
Phase 1
NCT03695380
Inclusion Criteria
• Ability to comply with the study protocol, in the investigator's judgment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient-reported outcome questionnaires
• Histological diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
• Previous treatment with a minimum of one and a maximum of two prior platinum based treatment regimens
• Platinum-sensitive disease
• Availability of tumor biopsy tissue prior to first dose of study treatment with confirmation by the central laboratory that the sample is not only of adequate quality but also assignable to a molecularly defined subgroup based on breast cancer susceptibility gene (BRCA) and loss of heterozygosity (LOH) status
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
• Adequate hematologic and organ function
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Resolved or stabilized toxicities resulting from previous therapy to Grade 1
• Negative HIV test at screening
• Negative hepatitis B surface antigen and total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL test at screening
• Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test at screening
• For women of childbearing potential: Women must remain abstinent or use two contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib, 6 months after the last dose of niraparib, and 5 months after the last dose of atezolizumab. Women must refrain from donating eggs during this same period Exclusion Criteria
• Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies
• Prior chemotherapy, hormonal therapy, radiotherapy, antibody therapy, or other immunotherapy, gene therapy, vaccine therapy, or treatment with experimental drugs within 14 days prior to first dose of study treatment
• Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study
• History of other malignancy that could affect compliance with the protocol or interpretation of results, or known to have potentially fatal outcome
• Symptomatic and/or untreated central nervous system metastases
• Surgical procedure, significant traumatic injury within 14 days prior to enrollment, or anticipation of need for major surgical procedure during the study
• Minor surgical procedure within 3 days
• History or evidence of retinal pathology on ophthalmic examination
• Left ventricular ejection fraction below institutional lower limit of normal
• History of clinically significant cardiovascular dysfunction
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the cobimetinib or niraparib formulation
• Active or history of autoimmune disease or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome, or multiple sclerosis
• Uncontrolled serious medical or psychiatric illness
• History of malabsorption or other condition that would interfere with absorption of oral study drugs, including preexisting duodenal stent or ongoing intestinal obstruction
• Active tuberculosis
• Severe infection within 14 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 7 days prior to initiation of study treatment
• Treatment with a live, attenuated influenza vaccine within 28 days prior to study treatment initiation, at any time during the study, and for at least 5 months after the last dose of study drug
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Previous treatment with strong CYP3A inhibitors (such as ketoconazole and clarithromycin), strong CYP3A inducers (such as carbamazepine and phenytoin), and moderate CYP3A inducers (such as efavirenz, modafinil) within 7 days prior to the initiation of study treatment or with ongoing requirements for these medications
• Pregnancy or breastfeeding, or intention to become pregnant during the study
• Ability to comply with the study protocol, in the investigator's judgment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient-reported outcome questionnaires
• Histological diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
• Previous treatment with a minimum of one and a maximum of two prior platinum based treatment regimens
• Platinum-sensitive disease
• Availability of tumor biopsy tissue prior to first dose of study treatment with confirmation by the central laboratory that the sample is not only of adequate quality but also assignable to a molecularly defined subgroup based on breast cancer susceptibility gene (BRCA) and loss of heterozygosity (LOH) status
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
• Adequate hematologic and organ function
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Resolved or stabilized toxicities resulting from previous therapy to Grade 1
• Negative HIV test at screening
• Negative hepatitis B surface antigen and total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL test at screening
• Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test at screening
• For women of childbearing potential: Women must remain abstinent or use two contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib, 6 months after the last dose of niraparib, and 5 months after the last dose of atezolizumab. Women must refrain from donating eggs during this same period Exclusion Criteria
• Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies
• Prior chemotherapy, hormonal therapy, radiotherapy, antibody therapy, or other immunotherapy, gene therapy, vaccine therapy, or treatment with experimental drugs within 14 days prior to first dose of study treatment
• Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study
• History of other malignancy that could affect compliance with the protocol or interpretation of results, or known to have potentially fatal outcome
• Symptomatic and/or untreated central nervous system metastases
• Surgical procedure, significant traumatic injury within 14 days prior to enrollment, or anticipation of need for major surgical procedure during the study
• Minor surgical procedure within 3 days
• History or evidence of retinal pathology on ophthalmic examination
• Left ventricular ejection fraction below institutional lower limit of normal
• History of clinically significant cardiovascular dysfunction
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the cobimetinib or niraparib formulation
• Active or history of autoimmune disease or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome, or multiple sclerosis
• Uncontrolled serious medical or psychiatric illness
• History of malabsorption or other condition that would interfere with absorption of oral study drugs, including preexisting duodenal stent or ongoing intestinal obstruction
• Active tuberculosis
• Severe infection within 14 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 7 days prior to initiation of study treatment
• Treatment with a live, attenuated influenza vaccine within 28 days prior to study treatment initiation, at any time during the study, and for at least 5 months after the last dose of study drug
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Previous treatment with strong CYP3A inhibitors (such as ketoconazole and clarithromycin), strong CYP3A inducers (such as carbamazepine and phenytoin), and moderate CYP3A inducers (such as efavirenz, modafinil) within 7 days prior to the initiation of study treatment or with ongoing requirements for these medications
• Pregnancy or breastfeeding, or intention to become pregnant during the study
Drug: Cobimetinib, Drug: Niraparib, Drug: Atezolizumab
Ovarian Cancer
Virginia Commonwealth University Stress Reduction Study
Hadley Rahrig, M.S. - rahrighm@mymail.vcu.edu
N/A
NCT04190030
Inclusion Criteria:
• Stable medication regiment for 8 weeks prior to enrollment if taking antidepressant or anxiolytic medications. (will not be advertised but screened)
• Free of major, uncorrected sensory impairments and cognitive deficits
• Free of a certain psychiatric disorders or history thereof; specifically, a new diagnosis of a (non-acute) medical or psychiatric condition within the last 3 months, report a hospitalization over the last 3 months, report current drug abuse (e.g., recreational drug use, alcohol intake in excess of 2 drinks per day).
• Adults aged 18 - 55 years of age
• Right hand dominant (will not be advertised but screened)
• Personal SmartPhone (Android or iOS operating systems).
• Naive to meditation practice (will not be advertised but screened)
• At least a moderate level of perceived stress (scale score > 5 on the 4-item Perceived Stress Scale (PSS; reflects above-average perceived stress)
Exclusion Criteria:
• left-handed
• are unwilling or unable to complete study assessments or treatments
• report a new diagnosis of a (non-acute) medical or psychiatric condition within the last 3 months
• report a hospitalization over the last 3 months
• report current drug abuse (e.g., recreational drug use, smoke more than ? pack per day, alcohol intake in excess of 2 drinks per day)
• are prisoners
• no personal SmartPhone (Android or iOS operating systems)
Behavioral: mindfulness training, Behavioral: cognitive reappraisal training
Stress
Mindfulness
The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-Versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant (MODULAATE)
Trial Registration Coordinator - clinicaltrials@cslbehring.com
Phase 2/Phase 3
NCT03805789
Inclusion Criteria:
• Male or female subjects, ?12 years of age (? 18 years of age for subjects at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome and myeloproliferative neoplasms
• Planned myeloablative conditioning regimen
Exclusion Criteria:
• Prior autologous or allogeneic HCT
• T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo (ie, anti-thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis
• Planned umbilical cord blood (UCB) transplant
Biological: Alpha-1 antitrypsin (AAT), Biological: Placebo
Acute-graft-versus-host Disease
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Madu, Mary, E - memadu@vcu.edu
Wang, Zhihong, Joanne
PHASE3
NCT04166409
HM20020781
Inclusion Criteria:
* Patients must be \>= 2 years and =\< 21 years at the time of enrollment
* Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
* Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Amendments (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
* Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
* Patients must have two-dimensional measurable tumor \>= 1 cm\^2 to be eligible
* Patients with ependymoma are not eligible
* Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
* Patients with metastatic disease or multiple independent primary LGG are eligible
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (performed within 7 days prior to enrollment):
* Age: Maximum Serum Creatinine (mg/dL)
* 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
* 6 to \< 10 years: 1 mg/dL (male); 1 mg/dL (female)
* 10 to \< 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
* 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect \[unconjugated\] bilirubin levels as long as their direct \[conjugated\] bilirubin is \< 3.1 mg/dL)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (performed within 7 days prior to enrollment)
* Left ventricular ejection fraction (LVEF) \>= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
* Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
* Absolute neutrophil count \>= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Platelets \>= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
* Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
* Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications)
* Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
* Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
* All patients must have ophthalmology toxicity assessments performed within 8 weeks prior to enrollment
* For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 8 weeks prior to enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have the ability to swallow whole capsules
* All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
* All patients and/or their parents or legal guardians must sign a written informed consent
* All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy \[LITT\]) is permitted
* Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
* Patients with diffuse intrinsic pontine tumors as seen on MRI (\> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
* Patients may not be receiving any other investigational agents
* Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
* Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
* Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are not eligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
* Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
* Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
* Symptomatic heart failure
* New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
* Severe valvular heart disease
* History of atrial fibrillation
* Current or past history of central serous retinopathy
* Current or past history of retinal vein occlusion or retinal detachment
* Patients with uncontrolled glaucoma
* If checking pressure is clinically indicated, patients with intraocular pressure (IOP) \> 22 mmHg or ULN adjusted by age are not eligible
* Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
* Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
* Note: Patients must have healed from any prior surgery
* Patients who have an uncontrolled infection are not eligible PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, DRUG: Selumetinib Sulfate, DRUG: Vincristine Sulfate
Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma
Pediatric KIDney Stone (PKIDS) Care Improvement Network (PKIDS)
Director of PKIDS Operations - pkids@chop.edu
Nelson, Eric
N/A
NCT04285658
HM20018357
Inclusion Criteria:
• Males or females, 8-21 years of age, undergoing planned URS, SWL, or PCNL for the removal of at least one kidney and/or ureteral stone.
• Parental/guardian or participant (if ≥ 18 years old) permission (informed consent), and if appropriate, child assent 2a. Individuals who are not able to provide consent/assent (whether ≥18 or < 18 years) and/or not willing or able to complete questionnaires are eligible for participation for the stone clearance assessment and Electronic Health Record (EHR) surveillance if the legal guardian consents for study participation. 2b. Individuals for whom native-language questionnaires are not available can also participate in stone clearance assessment and EHR surveillance.
Exclusion Criteria:
• Patients for whom conducting informed consent and baseline study procedures would confer additional risk (e.g. obstructing ureteral stone with fever requiring emergency surgery) and delay necessary immediate clinical care.
• Parent/guardians or patients, who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Procedure: Ureteroscopy, Procedure: Percutaneous Nephrolithotomy, Procedure: Shock Wave Lithotripsy
Kidney Stone, Nephrolithiasis
kidney, kidney stone, nephrolithiasis, Comparative Effectiveness, Patient Reported Outcomes
Reducing Error in ER Settings Through Attention Restoration Theory (RESTART)
Stephen Miller, DO - stephen.miller@vcuhealth.org
N/A
NCT04528862
Inclusion Criteria:
? Emergency Medicine Resident of any PGY level. (1-5)
Exclusion Criteria:
• Anybody under the age of 18
• Pregnancy
Behavioral: Nature slides, Behavioral: Urban slides
Attention Fatigue, Attention Restoration
A Study to Evaluate Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Participants With Childhood Epilepsy
Eisai Medical Information - esi_medinfo@eisai.com
PHASE2
NCT04015141
Inclusion Criteria:
* Male or female participants. Cohort 1: age 1 month to less than 18 years; Cohort 2: age 1 month to less than 2 years at the time of informed consent/assent. Participants below the age of 1 year must have been at least 36 weeks of gestational age at birth.
* Have a diagnosis of epilepsy with a pediatric epileptic syndrome (Cohort 1) or epilepsy with POS with or without secondary generalization (Cohort 2).
* Have had equal or greater than 4 seizures over the 4-week interval prior to enrollment visit.
* Absence of any progressive cause of epilepsy that has been confirmed clinically or based on brain imaging (example, magnetic resonance imaging \[MRI\] scan or computed tomography \[CT\] or ultrasound \[for less than 1 year old\]).
* Currently maintained on stable doses of 1 to a maximum of 4 approved antiepileptic drugs (AEDs). A prescription medical marijuana (including products containing cannabidiol) is counted as 1 of the maximum of 4 allowed AEDs; however, it cannot be the only concomitant AED if this product is not an approved AED in the country where the study site is located. Doses must be stable for at least 4 weeks (at least 2 weeks for participant less than \[\<\] 6 months old) before Visit 1/Baseline or screening; only 1 enzyme-inducing antiepileptic drug (EIAED) (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of 4 AEDs is allowed.
Exclusion Criteria:
* Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before screening visit.
* Have a history of status epilepticus that required hospitalization within 6 months before screening visit.
* Have an unstable psychiatric diagnosis that may confound participant's ability to participate in the study or that may prevent completion of the protocol specified tests (example, significant suicide risk, including suicidal behavior and ideation within 6 months before screening visit 1, current psychotic disorder, acute mania).
* Any suicidal ideation with intent with or without a plan within 6 months before enrollment visit (answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS) in participants aged 6 and above or based on the opinion of the Investigator for participants less than 6 years.
* Are scheduled or confirmed or both to have epilepsy surgery within 6 months after screening visit; however, those who have previously documented "failed" epilepsy surgery will be allowed.
* Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
* Benzodiazepines for any indications other than epilepsy (example, anxiety/sleep disorders) prohibited from 1 month before Visit 1/Baseline or screening and during the study. Benzodiazepines for seizure control and as rescue medication are allowed.
* A vagal nerve stimulator (VNS), responsive neurostimulator (RNS), or deep brain stimulator (DBS) implanted less than 5 months before screening visit or changes in parameter less than 4 weeks before screening visit (or thereafter during the study).
* Use of perampanel within 30 days before screening visit, or perampanel was discontinued due to adverse reactions (perampanel-related) or lack of efficacy in case of previous exposure.
* Weight less than 4.0 kilogram (kg) at Visit 1 (Baseline or screening). DRUG: Perampanel Oral Suspension, DRUG: Perampanel Tablet
Pediatric Epileptic Syndrome, Partial-onset Seizures
Partial-onset seizures, Pediatric epileptic syndrome, Epilepsy, Childhood epilepsy, Epilepsy in children, Refractory seizures, Inadequately controlled seizures, E2007, Fycompa, Perampanel
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) (MOVE FSHD)
Michaela Walker, MPH - mwalker20@kumc.edu
Johnson, Nicholas, E
N/A
NCT04635891
HM20021534
Inclusion Criteria:
* Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring.
Exclusion Criteria:
* Unwilling or unable to provide informed consent.
* Any other medical condition which in the opinion of the investigator would interfere with study participation. FSHD
Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation
Konrad S Famulski, PhD - konrad@ualberta.ca
NCT02670408
Inclusion Criteria:
* biopsy for clinical indications
Exclusion Criteria:
* no consent
* pregnant women PROCEDURE: Endomyocardial biopsy
Cardiac Transplant Disorder
Heart transplant, global gene expression, molecular diagnostics
Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM (EF-32)
Doron Manzur, MD - clinicaltrials@novocure.com
Harris, Timothy, James
N/A
NCT04471844
HM20024922
Inclusion Criteria:
• Histologically confirmed diagnosis of GBM according to WHO classification criteria.
• Age ≥ 22 years in US and Age ≥ 18 years in Ex-US
• Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
• Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2 daily x 5 d, q28 days)
• Karnofsky performance status ≥ 70
• Life expectancy ≥ least 3 months
• Participants of childbearing age must use highly effective contraception. An effective method of birth control is defined as one that results in a failure rate of less than 1% per year when used consistently and correctly. The Investigator must approve the selected method, and may consult with a gynecologist as needed.
• All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Stable or decreasing dose of corticosteroids for the last 7 days prior to randomization, if applicable.
• Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery
• Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to registration
• Is able to have MRI with contrast of the brain
Exclusion Criteria:
• Progressive disease (per investigator's assessment)
• Infratentorial or leptomeningeal disease
• Participation in another clinical treatment study during the pre-treatment and/or the treatment phase of the study
• Pregnancy or breast-feeding.
• Significant co-morbidities at baseline which would preclude maintenance RT or TMZ treatment, as determined by the investigator:
• Thrombocytopenia (platelet count < 100 x 103/μL)
• Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
• CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
• Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
• Total bilirubin > 1.5 x upper limit of normal
• Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)
• History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
• Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
• History of hypersensitivity reaction to TMZ or a history of hypersensitivity to DTIC.
• Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will be considered exclusion.
• Admitted to an institution by administrative or court order.
• Known allergies to medical adhesives or hydrogel
• A skull defect (such as, missing bone with no replacement)
• Prior radiation treatment to the brain for the treatment of GBM
• Any serious surgical/post-operative condition that may risk the patient according to the investigator
• Standard TTFields exclusion criteria include
• Active implanted medical devices
• Bullet fragments
• Skull defects
Device: Optune®
Glioblastoma Multiforme
GBM
Total Neoadjuvant Therapy With mFOLFOX and Short-course Radiation in Resectable Rectal Cancer
Massey IIT Research Operations, RN - masseyepd@vcu.edu
Matin, Khalid
PHASE2
NCT04643366
HM20020384
Inclusion Criteria:
* Pathologic diagnosis of adenocarcinoma of the rectum (diagnosis by tissue biopsy) within 90 days prior to registration. At least a portion of the tumor must be located below the peritoneal reflection or begin within 12 cm of the anal verge on flexible endoscopy
* Clinically staged (AJCC 8th ed.) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup:
* Colonoscopy, unless patient presents with an obstructing lesion
* Within 30 days prior to registration:
* History/physical examination
* Imaging to exclude distant metastases: either contrast-enhanced CT of the chest, abdomen, and pelvis or whole-body PET-CT or MRI
* Pelvic MRI (preferred) or transrectal ultrasound (TRUS) for T staging
* ECOG Performance Status ≤1
* Age ≥ 18 years
* Adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3
* Platelets ≥ 100,000 cells/mm3
* Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥8.0 g/dL is acceptable.)
* Adequate liver and renal function defined as follows:
* AST and alkaline phosphatase \< 2.5 x upper limit of normal (ULN)
* Bilirubin ≤ 2.5 ULN
* Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft-Gault formula as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine, and gender
* Must be deemed a candidate for curative resection by the surgical oncologist who will be performing the operation
* Women of childbearing potential (WCBP) must have a negative serum pregnancy test performed within 7 days prior to the start of chemotherapy.
* WCBP and men must agree to use a medically accepted form of birth control during the treatment and for 3 months following completion of chemotherapy.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Prior RT that would result in overlap of RT fields with the planned study treatment
* Clinically significant cardiac disease, including major cardiac dysfunction, that in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin.
* Serious (ie, ≥ grade 3) uncontrolled infection
* Pulmonary or respiratory condition that, in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin.
* Major surgery within 28 days of study enrollment (other than diverting colostomy)
* History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) requiring significant intervention (eg, hospitalization, surgery, immunosuppressive medications) that would, in the opinion of the investigator, preclude study therapy
* Prior known allergic reaction to 5-fluorouracil, leucovorin, or oxaliplatin
* Known dipyrimidine dehydrogenase deficiency (DPD)
* Any evidence of distant metastases (M1)
* Pregnant or breast feeding
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements DRUG: Chemotherapy, RADIATION: Radiation Therapy
Rectal Cancer
Resectable, Rectal
Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation (INTERLIVER)
Konrad S Famulski, PhD - konrad@ualberta.ca
N/A
NCT03193151
HM20012631
Inclusion Criteria:
* biopsy for clinical indications
Exclusion Criteria:
* no consent, pregnant women PROCEDURE: liver biopsy
Liver Dysfunction
Liver transplant, global gene expression, molecular diagnostics
Efficacy, Safety, And Pharmacokinetics Of Rifaximin In Subjects With Severe Hepatic Impairment And Hepatic Encephalopathy
Tendai Merriweather - tendai.merriweather@bauschhealth.com
Phase 4
NCT01846663
Inclusion Criteria:
• Male or non-pregnant, non-breast feeding female ≥ 18 years old
• In remission from demonstrated overt HE
• Had ≥1 episode of overt HE associated with liver disease within the last 6 months
• MELD score of ≥ 19
• Has a close family member or other personal contact who is familiar with the subject's HE, can provide continuing oversight to the subject and is willing to be available to the subject during the conduct of the trial
Exclusion Criteria:
• HIV
• History of tuberculosis infection
• Chronic respiratory insufficiency
• Current infection and receiving antibiotics
• Renal insufficiency requiring dialysis
• Active spontaneous bacterial peritonitis infection
• Intestinal obstruction or has inflammatory bowel disease
• Active malignancy within the last 5 years
• Current GI bleeding or has had a GI hemorrhage within past 3 months
• Anemia
Drug: Placebo, Drug: Rifaximin
Hepatic Encephalopathy
Hepatic Encephalopathy, Liver Failure, Hepatic Insufficiency, Liver Diseases, Brain Diseases, Rifaximin, Cirrhosis
NOURISH-T+: Promoting Healthy Eating and Exercise Behaviors (NOURISH-T+)
Marilyn Stern, PhD - mstern1@usf.edu
Mazzeo, Suzanne, E
NA
NCT04656496
HM20019104
Inclusion Criteria:
Eligible Pediatric Cancer Survivors must be:
• 5-14 years of age at enrollment;
• Off active treatment for at least 6 months;
• At or above the 85th BMI %ile;
• Able to complete assessments with the help of clinic staff and the USF research team;
• Residing with the participating parent;
• Able to engage in PA tailored to current medical status;
• NOT taking medications that affect body weight (e.g., steroids) within 6 months of enrollment, and
• In remission -- PCS who experience a relapse of cancer during the intervention will be excused from further involvement.
• Must be English- or Spanish-speaking Participating Parents must: * Be either biological or adoptive and/or step mothers or fathers and must be permanent legal guardians of the PCS * Be at least 18 years old * Identifies as the main meal preparer at home * Must be English- or Spanish-speaking
Exclusion Criteria:
* Parents are ineligible if they are non-ambulatory and/or do not reside at least 50% of the time with their participating child.
* Female parents who are currently pregnant will be excluded from the study.
* Children are ineligible to participate if they are non-ambulatory. In addition, children who are wards of the state will be excluded from the study. BEHAVIORAL: NOURISH-T+, BEHAVIORAL: Brief NOURISH-T+
Obesity, Childhood, Cancer, Survivorship
Chemotherapy Induced Peripheral Neuropathy Natural History Study (EPIPHANY) (EPIPHANY)
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or - ClinicalTrials.gov@lilly.com
Smith, Albert Gordon
N/A
NCT03997981
HM20016182
Inclusion Criteria:
All of the following criteria must be met in order to be enrolled in the study:
• Age ≥18 years
• Life expectancy ≥6 months
• Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 CIPN (exception, patients with multiple myeloma treated with bortezomib, CTCAE Grade <=1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Breast cancer only:
• Breast cancer beginning treatment with paclitaxel or docetaxel with curative intent (i.e., not metastatic disease beyond regional lymph nodes)
• Planned minimum of 6 cycles of chemotherapy
• Lymphoma only:
• Incident lymphoma initiating treatment with vincristine
• Planned minimum of 4 cycles of chemotherapy
• Oxaliplatin-based regimens, Stage III colorectal cancer: Total of 6 months (planned minimum of 12 cycles). May consider Stage IV with minimal metastatic confirmed with Sponsor prior to enrollment
• Bortezomib use in untreated multiple myeloma: Total of 4 months (planned minimum of 9 cycles)
• Written informed consent given
• Enrollment must be completed prior to receiving the first dose of chemotherapy
Exclusion Criteria:
Patients meeting ANY of the following criteria are not eligible for participation:
• Evidence of central nervous system metastases
• Evidence of clinically significant peripheral neuropathy (CTCAE >2) as defined by patient report of frequent numbness or tingling in the hands or feet
• Any uncontrolled serious illness or medical condition that would impact the conduct of the current study
• Previous exposure to neurotoxic chemotherapy drugs
• Pre-existing neurodegenerative disease (Parkinson's, Alzheimer's, Huntington's, etc.), neuromuscular disorder (multiple sclerosis, ALS, polio, hereditary neuromuscular disease) or history of stoke or history of traumatic brain injury
• General anesthesia less than one month prior to the first dose of neurotoxic chemotherapy
drug: Vincristine,
drug: Paclitaxel,
drug: Oxaliplatin,
drug: Docetaxel,
drug: Bortezomib
Chemotherapy-induced Peripheral Neuropathy
CIPN
Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC)
Pliant Therapeutics Medical Monitor - clintrials@pliantrx.com
Luketic, Velimir, A
Phase 2
NCT04480840
HM20019793
Inclusion Criteria:
• Established clinical diagnosis of large duct PSC based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic cholangiopancreatography (PTC) in the context of cholestatic liver chemistry
• Suspected liver fibrosis, as defined by liver stiffness measurement (LSM), assessed by ultrasound-based transient elastography (TE, FibroScan®) OR Enhanced Liver Fibrosis (ELF) Score OR Historical liver biopsy showing fibrosis without cirrhosis (by any scoring system) OR Magnetic resonance elastography (MRE)
• Serum ALP concentration within normal limits or > 1 times the upper limit of normal (ULN)
• Participants receiving treatment for IBD are allowed, if on a stable dose from screening and expected to remain stable for the duration of the study
• Serum AST and ALT concentration ≤ 5 times the upper limit of normal
• If receiving treatment with UDCA, therapy is at a dose of < 25 mg/kg/day, has been stable for at least 3 months before screening.
Exclusion Criteria:
• Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
• Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis
• Small duct PSC with no evidence of large duct involvement (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography)
• Presence of liver cirrhosis as assessed by liver histology, ultrasound-based liver stiffness measurement, ELF score, MRE, and/or signs and symptoms of hepatic decompensation (including but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy.
• Serum ALP concentration > 10 times the upper limit of normal.
Drug: PLN-74809, Drug: Placebo
Primary Sclerosing Cholangitis
Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD)
Katherine Wu, MD - kwu@jhmi.edu
NCT00733590
Inclusion Criteria:
* History of acute MI at least 4 weeks old
* Non-ischemic LV dysfunction for at least 9 months
* Who have an ejection fraction (EF) \< or = to 35%
* Undergone elective replacement indicator (ERI) generator replacement of an FDA-approved ICD for primary prevention of SCD within 24 months of enrollment.
* Who have primary prevention implants.
Exclusion Criteria:
* ICD generator replacement for secondary prevention
* Inability or unwillingness to provide valid informed consent
* New York Heart Association Class IV heart failure
* Patients with pre-existing Class 1 indications for pacemaker therapy. Heart Failure, Congestive, Death, Sudden, Cardiac, Arrhythmia, Cardiomyopathies
defibrillator, implanted, genomics, electrocardiography, electrophysiological study, proteomics
A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants
OHB Contact - CMO@Oakhillbio.com
Rozycki, Henry
PHASE2
NCT03253263
HM20016299
Inclusion Criteria:
• Written informed consents and/or assents must be signed and dated by the participant's parent(s) prior to any study related procedures. The informed consent and any assents for underage parents must be approved by the IRB/IEC (in accordance with local regulations).
• Written informed consents and/or assents must be signed and dated by the participant's birth mother prior to providing study-related information related to birth mother medical history, pregnancy and the birth of the participant. The informed consent and any assents for underage birth mothers must be approved by the IRB/IEC (in accordance with local regulations).
• Subjects must be between 23 weeks +0 days and 27 weeks +6 days GA, inclusive.
Exclusion Criteria:
• Detectable major (or severe) congenital malformation identified before randomization.
• Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator's opinion.
• Hypoglycemia at Baseline (blood glucose less than (\<) 45 milligrams per deciliter \[mg/dL\] or 2.5 milli moles per liter \[mmol/L\]) which persists in spite of glucose supplementation, to exclude severe congenital abnormalities of glucose metabolism.
• Clinically significant neurological disease identified before randomization according to cranial ultrasound (hemorrhages confined to the germinal matrix are allowed) and investigator's opinion.
• Any other condition or therapy that, in the investigator's opinion, may pose a risk to the participant or interfere with the participant's potential compliance with this protocol or interfere with interpretation of results.
• Current or planned participation in a clinical study of another investigational study treatment, device, or procedure (participation in non-interventional studies is permitted on a case-by-case basis).
• The participant or participant's parent(s) is/are unable to comply with the protocol or is unlikely to be available for long-term follow-up as determined by the investigator.
• Birth mother with active COVID-19 infection at birth or a history of severe COVID-19 infection (requiring intensive care hospitalization) during pregnancy.
• Birth mother with known HIV or hepatitis (B, C, or E) infection.
DRUG: OHB-607
Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity, Intraventricular Hemorrhage, Retinopathy of Prematurity (ROP)
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk)
Washington, Sonya, L - slwashington@vcu.edu
Sullivan, Stephanie, A
NA
NCT04251052
HM20020403
Inclusion Criteria:
* Individuals 35-50 years of age, inclusive
* Patients who will undergo risk-reducing salpingo-oophorectomy (RRSO) (for the BSO arm) and patients who have declined or elected to defer BSO after proper counselling to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned hysterectomy with either arm is permitted
* At least one intact ovary and fallopian tube is in situ at the time of counseling, consent, and registration. Prior hysterectomy is allowed provided it did not include bilateral salpingectomy. Prior tubal ligation is allowed if one ovary and fallopian tube (with fimbria not removed) are present
* Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation of the result is required
* Patients may be premenopausal or menopausal
* Pelvic ultrasound (transvaginal imaging preferred, but transabdominal imaging is acceptable) and CA-125 within 180 days of registration
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* Individuals who are currently pregnant or plan to become pregnant in the future through assisted reproductive technologies and who have received proper counseling are eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at the time of a planned cesarean section are eligible. Patients must understand that they will not be able to become pregnant naturally in the future
Exclusion Criteria:
* Individuals with a history of any prior cancer who have received cytotoxic chemotherapy within the past 30 days or radiotherapy to abdomen or pelvis at any prior time. Endocrine therapy or maintenance ERBB2/HER2 targeted therapy is allowed. Maintenance immune checkpoint inhibitor therapy is allowed. Maintenance therapy with PARP in inhibitor is allowed.
* Prior history of ovarian cancer, including low malignant potential neoplasms (LMP), primary peritoneal carcinoma, or fallopian tube carcinoma
* Patients medically unfit for the planned surgical procedure
* Patients with abnormal screening tests (pelvic ultrasound, CA-125) suspicious for occult or gross pelvic malignancy within the past 180 days
* An abnormal pelvic ultrasound is defined as morphologic or structural variations suspicious for ovarian malignancy. Complex cystic lesions felt to represent a benign lesion are not exclusionary. Simple cysts of any size are not exclusionary
* An abnormal CA-125 is defined as a level \> 50U/ml in premenopausal individuals if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level \> 40U/ml for premenopausal individuals who are current users of oral contraceptives (Skates 2011). An abnormal CA-125 is defined as a level \> 35 U/ml in postmenopausal individuals PROCEDURE: Bilateral Salpingectomy, PROCEDURE: Bilateral Salpingectomy with Oophorectomy, PROCEDURE: Biospecimen Collection, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, PROCEDURE: Transvaginal Ultrasound, PROCEDURE: Ultrasound Imaging
Ovarian Carcinoma
National Cancer Institute "Cancer Moonshot Biobank" (moonshot)
Castellanos, Natasha, Guzy - castellanosn@vcu.edu
Poklepovic, Andrew, S
N/A
NCT04314401
HM20020956
Inclusion Criteria:
* Is consistent with OR has been diagnosed with one of the following:
* Colorectal cancer: stage IV
* Non-small cell or small cell lung cancer: stage III/IV
* Prostate cancer: metastatic prostate cancer
* Gastric cancer, not otherwise specified (NOS): stage IV
* Esophageal cancer, NOS: stage IV
* Adenocarcinoma of gastroesophageal junction: stage IV
* High grade serous ovarian cancer: stage III/IV
* Invasive breast carcinoma: stage III/IV
* Melanoma: stage III/IV
* Acute myeloid leukemia
* Multiple myeloma
* For the purposes of this study,
* Re-staging is allowed
* Having more than one primary cancer is allowed, if the patient is being treated solely for one of the eligible cancers listed above
* Patient should fit in one of the following four clinical scenarios (a-d)
* Undergoing diagnostic workup for one of the diseases listed for which treatment will likely include a new regimen of standard of care therapy OR
* Scheduled to begin treatment with a new regimen of standard of care therapy OR
* Currently progressing on a regimen of standard of care therapy OR
* Currently being treated with a regimen standard of care therapy, without evidence of progression
* Requirements for fresh tissue biospecimen collections at enrollment:
* For clinical scenarios a, b, and c above, freshly collected tumor tissue or bone marrow (BM) aspirate must be submitted at enrollment
* For clinical scenarios a and b, the fresh tissue collection must be prior to starting therapy
* For clinical scenario a, the biospecimen collection must be part of a standard of care medical procedure
* For clinical scenarios b or c, the biospecimen collection may be part of a standard of care medical procedure OR
* The biospecimen collection may be part of a study-specific procedure ("research only biopsy"), when the patient has a tumor amenable to image guided or direct vision biopsy and is willing and able to undergo a tumor biopsy for molecular profiling
* Note: For research-only biopsies, the biopsy must not be associated with a significant risk of severe or major complications or death; the procedure cannot be a mediastinal, laparoscopic, open or endoscopic biopsy; nor can the procedure be a brain biopsy; nor can the patient be under the age of majority as determined by each U.S. state
* Requirements for archival tissue:
* For clinical scenarios a and b above, archival tissue as outlined below must be submitted IF AVAILABLE
* For clinical scenarios c and d above, archival tissue as outlined below is REQUIRED
* Pre-existing archival material (formalin-fixed, paraffin-embedded \[FFPE\] block, BM aspirate, or unstained slides) that:
* Contains the cancer type for which the participant is enrolled, and
* Was collected no more than 5 years prior to initiation of therapy, and
* Contains at least a surface area of 5 mm\^2 and optimal surface area of 25 mm\^2 or 3-5 mL cryopreserved bone marrow aspirate to yield 200 million bone marrow mononuclear cells, and
* Contains at least 10% tumor content. 70% tumor content is optimal, and
* No more than 1 line of standard of care systemic therapy was administered from the date of archival material collection to the date of initiation of therapy
* Requirements for blood collection: ALL scenarios require fresh blood collection at enrollment
* Blood collection for clinical scenarios a, b, and c must take place within 1 week of fresh tumor specimen collection
* Blood collection for clinical scenario d must take place within 4 weeks of enrollment, and while patient is on treatment
* Age 13 or older
* Any sex
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
* Ability to understand and willingness to sign an informed consent document. Consent may be provided by a Legally Authorized Representative (LAR) in accordance with 45 CFR 46.102(i)
* NCI PDMR INCLUSION CRITERIA: Patients with CRC with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status
* NCI PDMR INCLUSION CRITERIA: Patients with CRC who are 40 years old or younger at time of collection irrespective of mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status
* NCI PDMR INCLUSION CRITERIA: Patients with BRCA that are either
* Any race/ethnicity with hormone receptor positive (ER+PR+, ER+PR-, or ER-PR+)
* African American with triple negative (ER-PR-HER2-)
* NCI PDMR INCLUSION CRITERIA: Patients with lung cancer (LCA), prostate cancer (PCA), gastroesophageal cancer (GEC), ovarian cancer (OV), acute myeloid leukemia (AML), multiple myeloma (MML)
Exclusion Criteria:
* Treated with or has already begun treatment with a non-standard of care therapeutic agent (investigational) in an interventional clinical trial
* For the purposes of this study, past enrollment in clinical trials whereby the patient was randomized and treated with standard-of-care anti-cancer treatment (chemotherapy regimen, surgery and radiation therapy) is allowed
* Uncontrolled intercurrent illness that in the physician's assessment would pose undue risk for biopsy
* Use of full dose coumarin-derivative anticoagulants such as warfarin are prohibited. Patients may be switched to low molecular weight (LMW) heparin at physician discretion
* Low molecular weight (LMW) heparin is permitted for prophylactic or therapeutic use
* Factor X inhibitors are permitted
* Use of anti-platelet drugs are permitted
* Stopping the anticoagulation treatment for biopsy, bone marrow aspirate, or resection should be per site standard operating procedure (SOP)
* NCI PDMR EXCLUSION CRITERIA: Patients with complete response
* NCI PDMR EXCLUSION CRITERIA: Patients with invasive fungal infections
* NCI PDMR EXCLUSION CRITERIA: Patients with active and/or uncontrolled infections or who are still recovering from an infection
* Actively febrile patients with uncertain etiology of febrile episode
* All antibiotics for non-prophylactic treatment of infection should be completed at least 1 week (7 days) prior to collection
* No recurrence of fever or other symptoms related to infection for at least 1 week (7 days) following completion of antibiotics
* NCI PDMR EXCLUSION CRITERIA: Patients with human immunodeficiency virus (HIV), active or chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-deoxyribonucleic acid \[DNA\] and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]) or known history of HBV/HCV without documented resolution PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, OTHER: Medical Chart Review, PROCEDURE: Paracentesis, PROCEDURE: Positron Emission Tomography
Acute Myeloid Leukemia, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Esophageal Carcinoma, Fallopian Tube Carcinoma, Gastric Carcinoma, Hormone Receptor-Positive Breast Carcinoma, Invasive Breast Carcinoma, Lung Non-Small Cell Carcinoma, Lung Small Cell Carcinoma, Malignant Solid Neoplasm, Melanoma, Metastatic Prostate Carcinoma, Multiple Myeloma, Ovarian Carcinoma, Ovarian High Grade Serous Adenocarcinoma, Primary Peritoneal Carcinoma, Stage III Fallopian Tube Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Triple-negative Breast Carcinoma
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b
Jamie Barrett - medicalinformation@mersana.com
Randall, Leslie
Phase 1/Phase 2
NCT03319628
HM20020050
General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):
• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9 g/dL
• In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
• Estimated glomerular filtration rate (GFR) ≥45 mL/min
• Total bilirubin ≤ULN
• g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent. General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :
• Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
• Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Current use of either constant or intermittent supplementary oxygen therapy.
• History of suspected pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
• Oxygen saturation on room air <93% Ovarian Cancer Inclusion Criteria for UPLIFT:
• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.
• Platinum-resistant disease
• Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
• Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum
• One to 4 prior lines of systemic therapy for ovarian cancer a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure Ovarian Cancer Exclusion Criteria for UPLIFT:
• Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
• Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
• Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
• Participation in DES or EXP segments of this study Ovarian Cancer Inclusion Criteria for QTc sub-study: Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study • Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3. Ovarian Cancer Exclusion Criteria for QTc sub-study:
• Use of strong CYP450 3A inducers.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening with HR >45- <100
• Any ECG abnormality that can interfere with the measurement of the QT interval
• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9 g/dL
• In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
• Estimated glomerular filtration rate (GFR) ≥45 mL/min
• Total bilirubin ≤ULN
• g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent. General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :
• Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
• Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Current use of either constant or intermittent supplementary oxygen therapy.
• History of suspected pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
• Oxygen saturation on room air <93% Ovarian Cancer Inclusion Criteria for UPLIFT:
• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.
• Platinum-resistant disease
• Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
• Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum
• One to 4 prior lines of systemic therapy for ovarian cancer a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure Ovarian Cancer Exclusion Criteria for UPLIFT:
• Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
• Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
• Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
• Participation in DES or EXP segments of this study Ovarian Cancer Inclusion Criteria for QTc sub-study: Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study • Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3. Ovarian Cancer Exclusion Criteria for QTc sub-study:
• Use of strong CYP450 3A inducers.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening with HR >45- <100
• Any ECG abnormality that can interfere with the measurement of the QT interval
Drug: upifitamab rilsodotin
Platinum Resistant Ovarian Cancer, Non Small Cell Lung Cancer Metastatic
Cardiac Resynchronization Therapy in Previously Untreatable and High Risk Upgrade Patients (SOLVE-CRT)
Nicholas Vesom - clinical@ebrsystemsinc.com
Ellenbogen, Kenneth, A
N/A
NCT02922036
HM20014794
Inclusion/Exclusion:
Inclusion Criteria
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
Device: WiSE System
Heart Failure
STRIDE Biorepository
Lakshmanan Krishnamurti, MD - lakshmanan.krishnamurti@emory.edu
NCT02843347
Inclusion Criteria:
• Age at least 15 years old to less than 41 years old
• Severe sickle cell disease [any clinically significant sickle genotype, for example, Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb S?), or Hemoglobin S-OArab genotype] with at least 1 of the following manifestations:
• Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy);
• An average of three or more pain crises per year in the 2-year period preceding enrollment or referral (required intravenous pain management in the outpatient or inpatient hospital setting);
• Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year(in the 12 months before enrollment to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome);
• An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ?
• 7 m/sec;
• Ongoing high impact chronic pain on a majority of days per month for at least 6 months.
• Adequate physical function as measured by all of the following:
• Karnofsky/Lansky performance score > or equal to 60
• Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition (MUGA) Scan
• Pulmonary function: Pulse oximetry with a baseline O2 saturation of ? 85% and diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin)
• Renal function: Serum creatinine ? 1.5 x the upper limit of normal for age as per local laboratory and creatinine clearance >70 mL/min; or GFR > 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR)
• Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal as per local laboratory.
Exclusion Criteria:
• Human Leukocyte Antigen (HLA) typing prior to referral (consultation with hematopoietic cell transplantation (HCT) physician). However, if a subject has had HLA typing with accompanying documentation that relatives were not HLA typed and that a search of the unrelated donor registry was not performed the subject will be considered eligible. Documentation will be reviewed and adjudicated by the Protocol Officer or his/her designee.
• Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
• Seropositivity for HIV
• Previous HCT or solid organ transplant
• Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
• A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
• Demonstrated lack of compliance with prior medical care (determined by referring physician).
• Pregnant or breast feeding females.
• Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy. Additional Eligibility Criteria for Transplant after Biologic Assignment to the Donor Arm: Participants assigned to the Donor Arm at the time of biologic assignment are subject to additional transplant eligibility criteria as specified below. Additional, repeat clinical assessments prior to transplant should be obtained in accordance with institutional policies and standards of care in the interest of good clinical practice.
• Participants must have liver magnetic resonance imaging (MRI) (at least 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ?8 packed red blood cell transfusions for ?1 year or have received ?20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ?7 mg Fe/g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis, and active hepatitis (at least 90 days prior to initiation of transplant conditioning).
• Cerebral MRI/magnetic resonance angiogram (MRA) within 30 days prior to initiation of transplant conditioning. If there is clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) subjects will be deferred for at least 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation.
• Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications. This is to be documented in the medical record corresponding with the consent conference.
• Have a suitably matched HLA donor
• Willing and able to donate bone marrow
• Absence of anti-donor HLA antibodies
Procedure: Blood draw
Anemia, Sickle Cell
Biorepository, Genetics
PANTHER Study of Terumo Aortic Knitted and Woven Grafts, and Cardiovascular Patches (PANTHER)
Clinical Study Manager - r.smith1@terumoaortic.com
NCT04545502
Inclusion Criteria:
* Patients must meet all of the following inclusion criteria in order to be eligible for inclusion in the study:
All Patients:
* Patient meets the minimum age as per local regulations at time of consent
* Patient requires treatment with study device(s) according to the IFU(s)
* Patient is willing and able to comply with all SOC procedures and study visits
* Patient or their legally authorised representative (LAR) has given written informed consent to participate in study, including consent to collect data retrospectively
* For prospective emergency patients, retrospective consent is permissible
* For retrospective patients who are deceased at time of enrollment, local EC regulations relating to consent process should be followed.
Retrospective Patients only:
* Patient has a minimum of 1 year post-operative follow-up data available, or complete data to death.
* Patient implant date is no more than 5 years prior to study start date.
Exclusion Criteria:
* Any patient who meets any of the following exclusion criteria will be excluded from participation in the study:
* Patient is unable or unwilling to comply with the SOC procedures or follow-up regime
* Patient is contraindicated per the device IFU
* Patient has any other medical, social or psychological problems that in the opinion of the investigator preclude them from receiving this treatment and the procedures and evaluations pre- and post-procedure DEVICE: Gelsoft Plus Vascular Graft, DEVICE: Vascular Bypass Graft, DEVICE: Cardiovascular Patch, DEVICE: Gelweave Vascular Graft, DEVICE: Gelweave Valsalva Vascular Graft
Aneurysm, Dissection, Aortic Root Aneurysm, Aortic Root Dissection, Carotid Artery Injuries, Aortic Arch, Bypass Extremity Graft, Occlusive Vascular Disease, Aortic Diseases
Vascular Surgery
Testing the Addition of Radiation Therapy to the Usual Immune Therapy Treatment (Atezolizumab) for Extensive Stage Small Cell Lung Cancer, The RAPTOR Trial (RAPTOR)
Hamilton, Melanie, R - mrhamilton2@vcu.edu
Weiss, Elisabeth
PHASE2
NCT04402788
HM20020924
Inclusion Criteria:
* Any confirmation (cytologic, histologic, or pathologic) of extensive stage small cell lung cancer at any site, either primary or metastases
* Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography \[PET\]/computed tomography \[CT\] scan, diagnostic CT scan, magnetic resonance imaging \[MRI\] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum (if not receiving PCI) or 6 weeks from completion of prophylactic cranial irradiation (PCI)
* NOTE: Patients must have at least 3 cycles of E/P plus atezolizumab. They can have one cycle of induction E/P without concurrent atezolizumab if unable to receive concurrent E/P combined with atezolizumab for all cycles of induction therapy
* Patients must have measurable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment
* At time of enrollment after induction E/P chemotherapy and atezolizumab, if there is a pleural effusion, patients will be eligible if thoracentesis is cytologically negative or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
* Appropriate stage for study entry based on the following diagnostic workup:
* History/physical examination within 14 days prior to registration;
* Imaging within 42 days prior to registration to include:
* MRI brain with contrast or CT brain with contrast
* CT chest, abdomen and pelvis or whole body PET/CT scan any time after the fourth cycle of chemotherapy and prior to registration
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,000/cells/mm\^3 (within 14 days prior to registration)
* Platelets \>= 75,000 cells/mm\^3 (within 14 days prior to registration)
* Hemoglobin \>= 8 g/dL (within 14 days prior to registration)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN (AST and/or ALT =\< 5 ULN for patients with liver involvement) (within 14 days prior to registration)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration)
* Adequate renal function = Creatinine clearance \>=40 mL/min by the Cockcroft-Gault (C-G) equation: (within 14 days prior to registration)
* Upfront radiation therapy of symptomatic metastatic site is permissible if causing symptoms such as pain or impending fracture
* Patients with brain metastases are eligible after receiving whole brain radiation before enrollment (anytime during induction systemic therapy). Whole brain radiation can be delivered with hippocampal sparing or 3-D conformal technique. Patients with irradiated brain metastases are eligible if they are clinically stable from a neurological standpoint after completing radiotherapy (e.g. not having uncontrolled seizures) and do not require use of steroids above a dose of 10 mg of prednisone daily
* For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.
* Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
* Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
* Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months and a stable regimen of highly active anti-retroviral (HAART) HIV-positive patients must have no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Metastatic disease invading the liver (\> 3 metastases), heart or \> 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan counts as one site
* Patients with a concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen with atezolizumab or radiation
* Prior radiotherapy in the thorax that would result in overlapping RT fields, unless the overlapping fields meet acceptable dose constraints for normal tissue
* Active autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
* If the autoimmune disease is not active for over 3 years and the patient is not receiving immunosuppressive treatment such as methotrexate or steroids above a dose equivalent to 10 mg prednisone daily, the patient is eligible.
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
* Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations are excluded only if they have active disease with acute exacerbation and on immunosuppressive medications within the 12 months prior to enrollment. They are eligible otherwise.
* Severe, active co-morbidity defined as follows:
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
* Active tuberculosis;
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test)
* Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL);
* Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of \> 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary;
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months;
* History of recent myocardial infarction within 6 months prior to registration.
* Clinically significant interstitial lung disease
* Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Women who are breastfeeding and unwilling to discontinue
* History of allogeneic organ transplant
* Patients who have had immunotherapy-induced pneumonitis DRUG: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy
Extensive Stage Lung Small Cell Carcinoma
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
Donovan, Carrie - cdonovan2@vcu.edu
Myers, Jennifer, L
PHASE1
NCT04068194
Inclusion Criteria:
* PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced unresectable solid tumor that has progressed on or after available standard of care therapy or for which no acceptable standard of care therapy exists, or in which the patient declines standard of care therapy (each patient that declines standard of care therapy will be documented in the case report form)
* PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on gemcitabine, cisplatin, and durvalumab/pembrolizumab.
* Age \>= 18 years
* Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with avelumab in patients \< 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Patients with at least 1 index lesion to irradiate for whom palliative radiation treatment is indicated (including but not limited to pain and/or symptom control, prevention of disease -related complications, and preservation of organ function). Lung and liver lesions are preferred, though alternate lesions may be considered after discussion with trial principal investigator (PI). Up to 2 lesions may be considered for irradiation provided at least 1 lesion will receive the study treatment of total of 60 Gy and all prescribed irradiation will be completed within the radiation window
* Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesion (to be unirradiated) (defined as those accurately measured in at least one dimension, with the longest diameter to be recorded for non-nodal lesions and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph nodes
* Patients must be willing to undergo fresh biopsies at baseline (as opposed to using archival tissue), in the event their baseline tissue was obtained \> 12 months prior to study consent and/or they are randomized to the gamma H2AX, pNBS1 and pKAP1 IFA with beta CATN segmentation assay
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelet count \>= 100,000/mcL
* Hemoglobin \>= 9.0 g/dL
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine clearance (glomerular filtration rate \[GFR\] can be used in place of creatinine or creatinine clearance) \>= 60 mL/min for participants with creatinine levels \> 1.5 x institutional ULN
* Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
* Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< ULN for participants with total bilirubin \> 1.5 x ULN
* Patients with known Gilbert disease with serum bilirubin level =\< 3 x ULN are eligible
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN or =\< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
* Albumin \>= 2.8 g/L
* International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
* This applies only to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
* Participants must have the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption
* Female patients of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The effects of peposertib (M3814) and avelumab on the developing human fetus are unknown and there is the potential for teratogenic or abortifacient effects. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 6 months after completion of peposertib (M3814) and avelumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
* PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with the following exceptions:
* Patients who have only received previous durvalumab (anti-PD-L1) in combination with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen) are eligible
* Patients who have only received previous pembrolizumab (anti-PD-1) in combination with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966 regimen) are eligible
* Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 21 days of first planned dose of study therapy (within 14 days for palliative radiation). Previously irradiated lesions may be re-irradiated provided there is disease progression in the irradiated lesion and the prescribed radiation dosage can safely be re- administered
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1) with the exception of alopecia
* Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal disease. Patients with asymptomatic, treated CNS disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy and the following criteria are met:
* Radiographic demonstration of clinical stability upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study done \>= 4 weeks from completion of radiotherapy and \>= 2 weeks from discontinuation of corticosteroids
* No stereotactic radiation or whole-brain radiation within 28 days prior to randomization
* Patients with active autoimmune disease requiring systemic corticosteroids greater than the equivalent of prednisone 10 mg daily including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the following exceptions:
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only who require only low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
* Patients receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 6 weeks must discontinue these medications prior to starting peposertib (M3814) and avelumab on day 7, with the exception of:
* Patients with active autoimmune disease managed with systemic corticosteroids less than the equivalent of prednisone 10 mg daily
* Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea)
* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension and adrenocortical insufficiency
* Patients who have undergone prior solid organ or bone marrow transplant with the exception of patients with prior renal transplant for whom dialysis may be employed in the event of graft rejection
* Patients with uncontrolled intercurrent illness (e.g., including but not limited to uncontrolled hypertension \[HTN\] \[systolic blood pressure (BP) \> 150, diastolic BP \> 100\], symptomatic congestive heart failure \[CHF\], unstable angina pectoris, ischemic myocardial infarction \[MI\] within 6 months, cardiac arrhythmia, recent transient ischemic attack \[TIA or cerebrovascular accident (CVA)\]) within 6 months
* Patients with serious active infection (e.g. requiring hospitalization and/or intravenous \[IV\] antibiotics) within 4 weeks prior to starting peposertib (M3814) and avelumab, or signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of active systemic infection within 2 weeks prior to starting peposertib (M3814) and avelumab. Patients receiving prophylactic antibiotics are eligible
* Patients with known chronic hepatitis B virus (HBV) infection must have an undetectable viral load on suppressive therapy if indicated. Patients with known chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are currently on curative treatment are eligible if they have an undetectable HCV viral load
* Patients with known human immunodeficiency virus (HIV) are allowed on study provided they have:
* A stable regimen of highly active anti-retroviral therapy (HAART)
* No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infection
* A CD4 count above 250 cells/mcL
* An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based testing
* Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Patients with known concurrent malignancy that is expected to require active treatment within two years, or may interfere with the interpretation of the efficacy and safety outcomes of this study in the opinion of the treating investigator. Superficial bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring cytotoxic therapy should not exclude participation in this trial. Patients with chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active chemotherapy and their hematologic, renal and hepatic function meets criteria previously mentioned
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or avelumab
* Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting peposertib (M3814) and avelumab are ineligible. Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first peposertib (M3814) dose. Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as judged by the investigator must stop at least 1 day prior to first peposertib (M3814) dose. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. The primary elimination mechanism of avelumab is proteolytic degradation, thus there are no contraindicated medications with respect to avelumab
* Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to starting peposertib (M3814) and avelumab. These must be discontinued \>= 5 days prior to starting peposertib (M3814) and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers are allowed provided they are taken at least 2 hours after peposertib (M3814) dose
* Patients receiving sorivudine or any chemically related analogues (such as brivudine) and not able to discontinue prior to starting peposertib (M3814) and avelumab are excluded
* Pregnant and lactating women are excluded from this study because peposertib (M3814) and avelumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab
* Patients who have received live vaccination within 30 days before starting peposertib (M3814) and avelumab DRUG: Avelumab, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, RADIATION: Hypofractionated Radiation Therapy, DRUG: Peposertib
Locally Advanced Malignant Solid Neoplasm, Locally Advanced Unresectable Cholangiocarcinoma, Locally Advanced Unresectable Gallbladder Carcinoma, Locally Advanced Unresectable Malignant Solid Neoplasm, Metastatic Cholangiocarcinoma, Metastatic Gallbladder Carcinoma, Metastatic Malignant Solid Neoplasm, Stage III Gallbladder Cancer AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Unresectable Malignant Solid Neoplasm