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630 Study Matches
Feasibility and Acceptability of Using Weighted Blankets to Prevent and /or Mitigate Delirium
Heather Fudala, PhD - heather.fudala@vcuhealth.org
NCT06161480
Inclusion Criteria:
* 18 years of age or older.
* Requiring ICU level of care.
* Have a primary medical diagnosis.
* Proficient in English.
Exclusion Criteria:
* BMI less than 18.5.
* Significant deficit in cognitive functioning that is not expected to improve due to an end---stage disease stage or permanent injury (e.g., end-stage encephalopathy, traumatic or anoxic brain injury, dementia).
* Known pregnancy.
* Prisoners.
* Presence of skin injury (e.g., surgical wound, pressure injury, moisture injury) in an anatomical location where additional weight/pressure of blanket could prevent healing and /or lead to an expansion of the injury.
* Patients with skin injuries to areas easily left uncovered by the blanket (e.g., hands, feet) can be enrolled with additional communication to clinical team to leave areas uncovered to prevent additional injury.
* Paralysis effecting an area the weighted blanket will cover.
* Current neuromuscular blocking agent.
* Presence of recent/unhealed fractures on an area the blanket will cover (e.g., lower limb long bone, rib, pelvis, spine).
* History of claustrophobia reported by patient and/or their legally authorized representative (LAR).
* Fever of 37.5°C (99.5°F).
* Limited English proficiency. DEVICE: Weighted Blanket
Delirium
Screening for AL Amyloidosis in Smoldering Multiple Myeloma
Raymond Comenzo, MD - raymond.comenzo@tuftsmedicine.org
NCT06365060
Inclusion Criteria:
* Patients 40 years of age and older
* diagnosed with either Smoldering Multiple Myeloma or a Monoclonal Gammopathy
* dFLC greater than 23 mg/L
* abnormal FLC ratio
* If the patient has an eGFR less than 50 mL/min/1.73m2, the FLC ratio is inconsequential. The patient only needs to meet the age and dFLC criterion.
Exclusion Criteria:
* Patients younger than 40 years of age are not eligible
* Patients with a previous finding of amyloid in other biopsies will not be included
* Adults unable to consent are not eligible, including the cognitively impaired Pregnant women, pregnant minors, minors (i.e., individuals who are not yet adults), wards of the state, non-viable neonates, neonates of uncertain viability, and prisoners are not eligible Smoldering Multiple Myeloma
SMM, AL Amyloidosis
Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis (AMS05)
ctrrecruit@vcu.edu
NCT05285891
Inclusion Criteria:
• Have at least one clinical episode that satisfies McDonald 2017 criteria for early Multiple sclerosis (MS) for up to 2 years post-event with a dissemination in time that can be met clinically, by Magnetic Resonance Imaging (MRI), or based on oligoclonal band (OCB) positivity
• Have a length of disease duration, from first symptom, of ≤ 2 years
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use effective methods of contraception during the treatment period and for at least 6 months after the last dose of study drug:
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods include bilateral tubal ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices, and copper intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception
• Barrier methods must always be supplemented with the use of a spermicide
Exclusion Criteria:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• History of Primary Progressive Multiple Sclerosis (PPMS), Progressive Relapsing Multiple Sclerosis (PRMS), or Secondary Progressive Multiple Sclerosis (SPMS)
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing Magnetic resonance imaging (MRI)
• Known presence or history of other neurological disorders, including but not limited to the following:
• Ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
• Central Nervous System (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
• Pregnancy or lactation a. Female participants of childbearing potential must have a negative urine pregnancy test at screening
• Any concomitant disease that may require chronic systemic treatment with corticosteroids or immunosuppressants during the course of the study
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant, inadequately controlled (e.g. diagnostic evaluations indicated or change in medications warranted) disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that in the opinion of the investigator may preclude participant from participating in the study
• Functional status of NY Heart Association (NYHA) Class III or higher for heart failure at the screening visit
• Known active bacterial, viral, fungal, mycobacterial infection or other infection (including tuberculosis \[TB\] or atypical mycobacterial disease but excluding limited superficial fungal or viral infections of the skin or nails) or any severe episode of infection requiring hospitalization or treatment with Intravenous (IV) antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
• Active or chronic infection with Human Immunodeficiency Virus (HIV), syphilis or TB (see laboratory tests below)
• 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
• Known active malignancy or active monitoring for recurrence of malignancy, including solid tumors and hematological malignancies, except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix or the uterus that have been excised with clear margins
• Substance use disorder, including the recurrent use of alcohol and/or drugs within the past year associated with clinically significant impairment associated with failure to meet major responsibilities at work, school, or home
• Receipt of live or live-attenuated vaccines within 4 weeks prior to baseline
• Contraindications to or severe intolerance of oral or IV corticosteroids, including Intravenous (IV) methylprednisolone administered according to the country label, including:
• Psychosis not controlled by a treatment
• Hypersensitivity to any of the constituents or excipients of the preceding steroids
• Current or prior treatment with the following MS DMTs: fingolimod and other S1P receptor modulators, cladribine, natalizumab, anti-CD20 molecules, alemtuzumab, and chemotherapeutic agents
• Treatment with fumarates within 30 days prior to baseline
• Current or prior treatment with any experimental therapies (e.g., bone marrow transplant), investigational agent, or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
• Systemic corticosteroid therapy within 4 weeks prior to screening
• Laboratory test results as follows: a. Positive infection screening tests for: i. Hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) ii. Hepatitis C (HCV) antibody, if positive screen for HCV RNA Polymerase Chain Reaction (PCR) iii. Rapid plasma reagin (RPR) iv. HIV v. At or within twelve months of screening: * Positive QuantiFERON(R)-TB Gold test or positive purified protein derivative tuberculin skin test (PPD) (\>5mm induration, regardless of Bacille Calmette Guerin \[BCG\] vaccine administration) unless completion of treatment has been documented for active TB * An indeterminate QuantiFERON(R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department b. Levels of serum immunoglobulin G (IgG) \< 3.3g/L c. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>= 2.0 x the upper limit of normal (ULN) e. Platelet count \< 100,000 plt/mcL (\< 100 x 10\^9/L) f. Hemoglobin \< 10 g/dL g. Absolute neutrophil count \< 1.5 × 10⁹/L h. Absolute lymphocyte count \< 1.2 x 10⁹/L
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
DRUG: Ocrelizumab, DRUG: Placebo for Ocrelizumab
Multiple Sclerosis
Ocrelizumab, Multiple sclerosis, Relapse
Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age with Relapsed/Refractory CBFA2T3::GLIS2 AML
Anna Butturini, MD - CBFGLISAML@sutrobio.com
NCT06679582
Inclusion Criteria:
* AML with CBFA2T3::GLIS2 gene fusion centrally confirmed
* Refractory or relapsed disease with ≥ 5% bone marrow involvement with leukemic blasts by morphology
* Age \< 12 years.
* Lansky performance of ≥ 50
* Adequate organ functions
Exclusion Criteria:
* Active central nervous system (CNS) disease (CNS3)
* Pre-existing clinically significant corneal disorders or constitutional diseases associated with an increased risk of AML treatment toxicities
* Active or uncontrolled infections or other active severe intercurrent illnesses,
* Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor
* History of allogeneic hematopoietic stem cell transplant or any organ transplant in the prior 84 days
* Graft versus host disease (GVHD) of any grade or GVHD treatment with exception of low dose steroids DRUG: Luveltamab tazevibulin
Acute Myeloid Leukemia (AML)
CBFA2T3::GLIS2 Fusion, CBFA2T3::GLIS2 AML, RAM Phenotype (CD56pos), CD45, CD38, HLA-DR weak or absent), REFRaME, AML, Child, Pediatric AML, Levelatamab, REFRaME-P1
ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND) (ASCEND)
Kelli McDonough, MS - kellimcd@umich.edu
NCT05388708
Inclusion Criteria:
* Time between intubation and ECMO cannulation is less than 240 hours (10 days)
* ECMO support type is respiratory (VV or VA cannulation)
* Chest radiograph with bilateral lung disease
* Moderate or severe pediatric ARDS as measured by oxygenation index or oxygen saturation index after intubation and prior to ECMO cannulation:
One OI ≥ 16 or Two OIs ≥ 12 and ≤ 16 at least four hours apart or Two OSIs ≥ 10 at least four hours apart or One OI ≥ 12 and ≤ 16 and One OSI ≥ 10 at least four hours apart
Exclusion Criteria:
* Previously enrolled in PROSpect
* Perinatal related lung disease
* Congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis
* Respiratory failure caused by cardiac failure or fluid overload
* Cyanotic congenital heart disease
* Cardiomyopathy
* Primary pulmonary hypertension (PAH)
* Unilateral lung disease
* Intubated for status asthmaticus
* Obstructive airway disease
* Bronchiolitis obliterans
* Post hematopoietic stem cell transplant
* Post lung transplant
* Home ventilator dependent
* Neuromuscular respiratory failure
* Head trauma: (managed with hyperventilation)
* Intracranial bleeding
* Unstable spine, femur or pelvic fractures
* Acute abdominal process/open abdomen
* Family/medical team have decided to not provide full support
* Enrolled in interventional clinical trial: not approved for co-enrollment; does not include cancer protocols.
* Known pregnancy DEVICE: ECMO support, OTHER: PROSpect protocolized therapies
Acute Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation
ARDS, Acute Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation, ECMO, Extracorporeal Life Support, ECLS, Pediatric, Quality of Life, Functional Status
Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
ctrrecruit@vcu.edu
NCT05721755
Inclusion Criteria:
* STEP 1 REGISTRATION:
* Patient must be \>= 18 years of age
* Patient must have biopsy-proven metastatic squamous cell carcinoma, originating in the oral cavity, larynx, oropharynx, or hypopharynx, with active disease present in both the head and neck and distant sites
* NOTE: The tumor from an oropharynx primary site must have known p16 status; p16 positive cancer of unknown primary is allowed as well, provided the disease presentation in consistent with a head and neck primary
* Patient can have prior surgical resection of a primary cancer in the head and neck at any previous time, however, residual/recurrent disease in the head and neck must be present on baseline imaging
* Any effects from prior cancer therapy for other diseases must be fully resolved and not pose a problem for giving the treatment on this trial
* Patient must have 4 or fewer metastatic sites prior to starting any treatment, with thoracic nodal disease considered a single site if encompassable in a tolerable radiotherapy hypofractionated field (i.e.,15 fractions or less)
* NOTE: Contiguous/adjacent metastases treatable in a single stereotactic field may be considered a single site
* NOTE: Patients with additional indeterminate findings such that the total number of metastatic sites would be more than 4 may be enrolled if a non-malignant etiology to these findings is a reasonable consideration
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patients must have measurable disease as follows:
* For patients who have not started any initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck and chest, and abdomen obtained within 28 days prior to Step 1 registration
* For patients who have started or completed their 3 cycles of initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck, chest and abdomen obtained within 28 days prior to the start of their initial systemic therapy
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Total bilirubin =\< institutional upper limit of normal (ULN). Patients with a total bilirubin \> 1.5 x ULN, that is attributed to confirmed Gilbert's syndrome, are allowed after consultation and approval from their treating physician (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Creatinine clearance: Glomerular filtration rate (GFR) \>= 50 mL/min/1.73m\^2 (for patients receiving carboplatin-based regimens, GFR \> 30 mL/min/1.73m\^2) (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients on Arm S must have received chemoimmunotherapy
* Patients will be enrolled in the quality of life (QOL) study if the patient can read and understand English, Spanish, French or Chinese (simplified or traditional characters)
* NOTE: Sites cannot translate the associated QOL forms
* Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive measures for 4 months after the last dose of protocol treatment and must not breastfeed while on study treatment through 4 months after the last dose of protocol treatment
* STEP 2 RANDOMIZATION:
* Patient must have ECOG performance status 0-2
* Patient must have completed 3 cycles of initial systemic chemotherapy
* For patients registered to Arm S on Step 1, patients must have at least stable disease after completing 3 cycles of pembrolizumab + chemotherapy
* Patient must have no signs of progression (complete response \[CR\]/partial response \[PR\] or stable disease \[SD\]) on restaging imaging (consisting of neck, chest, and abdomen CT). Restaging imaging must have been done after completion of initial systemic chemotherapy with pembrolizumab + chemotherapy on Step 1 and within 7 days prior to step 2 randomization. Patients with stable or responding radiologic response are eligible for Step 2
Exclusion Criteria:
* Patients must not have prior head and neck radiotherapy
* Patient must not have an active autoimmune disease (i.e., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc.) that has required systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) in past 2 years. Replacement therapy (i.e., thyroxine, insulin, physiologic corticosteroid replacement) is not considered a form of systemic treatment and is allowed
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not have received any live vaccine within 30 days prior to Step 1 registration and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist trademark are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Fluorouracil, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Sinusitis (NOSES)
Lead Project Coordinator - researchfammed@georgetown.edu
NCT06076304
Inclusion Criteria:
• 18-75 years old; AND are experiencing either:
• "persistent" symptoms or signs compatible with ARS or sinus infection lasting for 1-21 days without any evidence of clinical improvement (Symptoms include facial pain or pressure, facial congestion or fullness, nasal obstruction, nasal discharge, no or reduced sense of smell, fever ≤39°C or 102°F, headache, bad smelling breath, fatigue, ear pain or pressure, and dental pain); OR
• onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5-6 days and were initially improving (''double-sickening'').
Exclusion Criteria:
* allergy or intolerance to penicillin
* received systemic antibiotic therapy in the past 4 weeks
* prior sinus surgery (cosmetic surgery, such as rhinoplasty, septal deviation, etc. are not exclusionary)
* complications of sinusitis (facial edema (swelling), cellulitis), or orbital, meningeal or cerebral signs)
* health care clinician determined IV (intravenous) antibiotics or hospital admission are required
* pregnancy or breastfeeding
* presence of a comorbidity or medication that may impair a patient's immune response as determined by a health care clinician
* hospitalization in past 5 days
* unable or unwilling to provide informed consent or comply with study protocol requirements
* fever \>39°C or 102°F today
* taking intranasal corticosteroids (INCS) regularly in the past two weeks and unwilling to stop its use while in the study; OR
* previously enrolled or participated in the feasibility phase or this stage of study DRUG: Amoxicillin/Clavulanate Potassium 875 MG-125 MG Oral Tablet, DRUG: Placebo, DRUG: Budesonide nasal spray, OTHER: C-reactive protein
Sinus Infection, Acute Sinusitis
sinusitis, antibiotics, intranasal corticosteroids, saline nasal irrigation, comparative effectiveness
Feasibility Study for the Comprehensive Overweight/Obesity Management Pre-Kidney Transplant (COMPKT) Program
Evan Sisson - emsisson@vcu.edu
NCT06688825
Inclusion Criteria:
* on the waiting list for kidney transplant at VCUHS
* BMI greater than 35 kg/m2
Exclusion Criteria:
* Children, prisoners, pregnant women BEHAVIORAL: Education regarding Weight loss, BEHAVIORAL: Lifestyle tools for weight loss, BIOLOGICAL: Blood draw
Kidney Transplant, Complications, Obesity
Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)
Jennifer Raymond - Jennifer.Raymond@vcuhealth.org
NCT05989620
Inclusion Criteria:
• Age between 6-50 years at enrollment
• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with proximal weakness)
• Genetic confirmation of a LGMD, DM2, or LOPD
• FVC above 30% of predicted
Exclusion Criteria:
• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator
• Participation in a clinical trial receiving an investigational product
LGMD1B, LGMD1C, LGMD1D, LGMD1E, LGMD1F, LGMD1G, LGMD1H, LGMD2A, LGMD2B, LGMD2C, LGMD2D, LGMD2E, LGMD2F, LGMD2G, LGMD2I, LGMD2J, LGMD2K, LGMD2L, LGMD2M, LGMD2N, LGMD2O, LGMD2P, LGMD2Q, LGMD2S, LGMD2T, LGMD2U, LGMD2W, LGMD2X, LGMD2Y
Muscular Dystrophy, Myotonic Dystrophy, Limb Girdle Muscular Dystrophy, LGMD, LOPD, Late Onset Pompe Disease
Functional Outcomes in CondUction System Pacing and Right Ventricular Synchrony (FOCUS-Right) (FOCUS-Right)
Ajay Pillai - ajay.pillai@vcuhealth.org
NCT06601322
Inclusion Criteria:
* presence of dual chamber LBBAP implantation
* presence of anodal capture with bipolar pacing configuration as determined at pacing implant.
Exclusion Criteria:
* Known history of chronotropic incompetence
* high degree or complete heart block
* inability to tolerate NVP during initial device interrogation
* pregnancy
* inability to undergo MRI or exercise utilizing supine bicycle at target work-load
* presence of MRI unsafe pacemaker components. OTHER: Pacemaker Interrogation and Electrocardiogram (ECG):, OTHER: Cardiopulmonary Exercise Test (CPET) and Exercise Stress Cardiac Magnetic Resonance (ExeCMR, OTHER: Continuous pacemaker telemetry (CPT)
Left Branch Bundle Block, RV - Right Ventricular Abnormality
Pacemaker, CPET-CMR
Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion
Tiffany Pignatello - Tfitz@vcu.edu
NCT05976646
Inclusion Criteria:
* Males and female subjects between 18 - 65 years of age;
* Understand the study procedures and provide written informed consent in the English language.
* Meet current DSM-5 criteria for OUD, of at least moderate severity, currently engaged in MOUD treatment at a buprenorphine-naloxone sublingual film total daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 daily for at least 2 weeks at screening. Or on a stable dose of depot injectable buprenorphine for at least four months, with at least one week since last depot buprenorphine injection.
* Have a positive urine drug screen for buprenorphine during screening and upon presenting for the first laboratory day on the clinical research unit to document buprenorphine use;
* Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or greater (\>6)
* Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (ie., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal), participants must agree to use an acceptable form of contraception during study participation and to continue its use for at least 30 days after the last dose of the study drug (e.g, abstinence, intrauterine device, hormonal implant, hormonal patch/ring/pill, condoms (male or female).
Exclusion Criteria:
* Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
* Pregnant or nursing women;
* Baseline ECG with clinically significant abnormal conduction;
* Uncontrolled serious psychiatric or major medical disorder; including uncontrolled hypertension, seizure disorder, anorexia nervosa or bulimia, bipolar disorder, schizoaffective disorder, or schizophrenia;
* Taking antidepressant medications (tricyclic antidepressants, SSRIs, SNRIs, MAOIs), antibiotic linezolid, antiepileptics, or CNS stimulants (amphetamine, methylphenidate) within the two weeks prior to initiation of study medication
* History of adverse reaction or allergy to dextromethorphan or bupropion
* Current severe alcohol use disorder or current benzodiazepine use or recent (within last 3 months) discontinuation of alcohol with severe alcohol use disorder or discontinuation of benzodiazepines with severe benzodiazepine use disorder
* Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
* Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
* Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. DRUG: Placebo, DRUG: Auvelity
Addiction, Opioid Use, Substance Use Disorders, Opioid Use Disorder
Lived Experiences of Black Girls in Richmond
Yali Pang, PhD - pangy@vcu.edu
NCT05858281
Inclusion Criteria (Online Survey and focus groups):
* Self-identify as Black/African American adolescent cisgender girls, between the ages of 12-17, and reside in the City of Richmond.
Exclusion Criteria (Online Survey and focus groups):
* Girls who are not between 12 to 17 years of age, do not self-identify as Black, does not identify as cisgender, legal residence is not located in the city of Richmond, and/or who do not read English.
Inclusion Criteria (Interviews):
* Parents/guardians (any sex; no age range for parent/guardian) of Black girls (ages 12-17) who reside in the City of Richmond; and
* Black emerging adult women (ages 18-22) who resided in the City of Richmond when they were under 18.
Exclusion Criteria (Interviews):
* Parent/Guardian - Does not have a child (daughter) between the ages of 12-17; child does not self-identify as cisgender and Black/African American; legal residence is not in the city of Richmond; unable to read, write, or speak in English.
* Emerging adult women - does not self-identify as Black/African American, under 18 or over the age of 22, did not reside in the City of Richmond under 18, and unable to read, write, or speak in English.
BEHAVIORAL: Survey, BEHAVIORAL: Interviews, BEHAVIORAL: Focus group
Lived Experiences, Strengths, and Community Assets of Black Girls
Brain Oxygen Optimization in Severe TBI, Phase 3 (BOOST3)
William Barsan, MD - wbarsan@umich.edu
NCT03754114
Inclusion Criteria:
* Non-penetrating traumatic brain injury
* Glasgow Coma Scale (GCS) 3-8 measured off paralytics
* Glasgow Coma Scale motor score \< 6 if endotracheally intubated
* Evidence of intracranial trauma on CT scan
* Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
* Able to place intracranial probes and randomize within 12 hours from injury
* Age greater than or equal to 14 years
Exclusion Criteria:
* Non-survivable injury
* Bilaterally absent pupillary response in the absence of paralytic medication
* Contraindication to the placement of intracranial probes
* Treatment of brain tissue oxygen values prior to randomization
* Planned use of devices which may unblind treating physicians to brain tissue hypoxia
* Systemic sepsis at screening
* Refractory hypotension
* Refractory systemic hypoxia
* PaO2/FiO2 ratio \< 150
* Known pre-existing neurologic disease with confounding residual neurological deficits
* Known inability to perform activities of daily living (ADL) without assistance prior to injury
* Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
* Pregnancy
* Prisoner
* On EFIC Opt-Out list as indicated by a bracelet or medical alert OTHER: ICP + PbtO2 guided management strategy, OTHER: ICP guided management strategy
Brain Injuries, Traumatic
intracranial pressure, hypoxia, brain, critical care, emergency treatment, monitoring, physiologic
A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma
Project Director - medicalaffairs@zentalis.com
NCT04814108
INCLUSION CRITERIA
• Females ≥18 years of age at the time of informed consent.
• Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject. * Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible. * Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
• Measurable disease per RECIST Guideline Version 1.1
• Required prior therapy for endometrial cancer:
• Treatment with a platinum-based chemotherapy regimen.
• Treatment with a PD-(L)1 inhibitor
• Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
• Adequate hematologic and organ function EXCLUSION CRITERIA
• Any of the following treatment interventions within the specified time frame prior to C1D1:
• Major surgery within 28 days
• Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
• Radiation therapy within 21 days;
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
• Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
• A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.
• Females ≥18 years of age at the time of informed consent.
• Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject. * Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible. * Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
• Measurable disease per RECIST Guideline Version 1.1
• Required prior therapy for endometrial cancer:
• Treatment with a platinum-based chemotherapy regimen.
• Treatment with a PD-(L)1 inhibitor
• Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
• Adequate hematologic and organ function EXCLUSION CRITERIA
• Any of the following treatment interventions within the specified time frame prior to C1D1:
• Major surgery within 28 days
• Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
• Radiation therapy within 21 days;
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
• Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
• A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.
DRUG: ZN-c3
Uterine Serous Carcinoma
uterus, uterine, endometrial, endometrium, serous carcinoma, wee1, Wee-1, usc, Uterine Serous Carcinoma, serous
Pre-Operative Window of ET to Inform RT Decisions (POWER II) (POWER II)
Meagan Miller - aey8fc@uvahealth.org
NCT06507618
Inclusion Criteria (summary):
* Diagnosis of ER+, PR +/-, and HER2- non amplified invasive breast cancer and clinically negative nodes
* ECOG performance status 0-2
* Females, aged ≥ 65 years
* Patient is eligible for BCS and opted for BCS
* Patient is a candidate for radiation therapy
* Patient is a candidate for endocrine therapy (tamoxifen or an aromatase inhibitor)
* Ability to take oral medication and be willing to adhere to endocrine therapy for the 3-month period prior to BCS
* Agreement to adhere to Lifestyle Considerations (details in protocol) throughout study duration
* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria:
* Bilateral synchronous breast cancer
* Multicentric disease
* Prior use of SERMS or aromatase inhibitors
* History of ipsilateral breast radiation therapy
* Has a known additional malignancy that is progressing and/or requires active treatment with cytotoxic chemotherapy or radiation therapy. Malignancies deemed stable and low risk for complication per investigator's judgment may be allowed after discussion with multi-site PI.
* Current or planned use of a strong CYP2D6 inhibitor (e.g., Fluvoxamine, Paroxetine) and is not able to receive an endocrine therapy agent that does not use the CYP2D6 pathway. DRUG: Tamoxifen, Letrozole, Anastrozole, or Exemestane
Breast Cancer Female
breast cancer, endocrine therapy, radiation, letrozole, anastrozole, exemestane, tamoxifen, survey, questionnaire, geriatric
Testing Whether the Addition of Carboplatin Chemotherapy to Cabazitaxel Chemotherapy Will Improve Outcomes Compared to Cabazitaxel Alone in People With Castrate-Resistant Prostate Cancer That Has Spread Beyond the Prostate to Other Parts of the Body
ctrrecruit@vcu.edu
NCT06470243
Inclusion Criteria:
* STEP 1 SCREENING REGISTRATION: NOTE: All participants must have biopsy tissue submitted to MD Anderson Cancer Center prior to randomization for alteration assessment. Participants must have determination of their AVPC-Molecular Pathologic Signature immunohistochemistry (MSIHC) status from central assessment by the MD Anderson Clinical Pathology Laboratory using Clinical Laboratory Improvement Act (CLIA) certified immunohistochemistry (IHC) assays for TP53, RB1 and PTEN. In addition, while not mandated, CLIA certified next generation sequencing (NGS) of tumor deoxyribonucleic acid (DNA) and/or circulating tumor derived DNA (ctDNA) assessment of AVPC-MS marker status will be collected from participants for whom it is available
* STEP 1 SCREENING REGISTRATION: Participants must have a histologically confirmed diagnosis of prostate cancer at the time of step 1 registration
* STEP 1 SCREENING REGISTRATION: Participants must have castrate-resistant prostate cancer and metastatic disease by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node)
* STEP 1 SCREENING REGISTRATION: Participants may have received any prior therapy, but one must be docetaxel or contain docetaxel in either the castrate-sensitive and/or castrate resistant disease state
* STEP 1 SCREENING REGISTRATION: Participants must be ≥ 18 years of age at the time of step 1 screening registration
* STEP 1 SCREENING REGISTRATION: Participants must have solid tumor biopsy material (formalin-fixed paraffin-embedded (FFPE) tissue blocks and/or 10 cut slides on four-micron thick unstained positive charged slides of FFPE tissue) available for submission for alterations in TP53, RB1 and PTEN by IHC using CLIA certified assays in the MD Anderson Clinical Pathology Laboratory. This specimen is required for central assessment of the AVPC-MSIHC regardless of whether the site has already locally evaluated the AVPC-MS status
* STEP 1 SCREENING REGISTRATION: Tumor samples submitted for analysis must have been collected within 12 months prior to step 1 screening registration. Samples from metastatic lesions collected in the castrate-resistant disease state are preferable but not mandatory. Samples obtained during the hormone-naive disease state are acceptable if collected within 12 months of step 1 screening registration. If more than one tumor sample exists, the sample obtained closest to the date of registration should be submitted to MDACC for analysis
* NOTE: Sites will receive an email from Southwest Oncology Group (SWOG) Statistics and Data Management Center containing participant results of Aggressive Variant Prostate Cancer Molecular Signature (AVPC-MS) assessment within 5-12 business days after tissue submission to MD Anderson Clinical Pathology Laboratory. The participant's AVPC-MS signature result (positive or negative) is required BEFORE randomization on to step 2. If sites receive a non-evaluable AVPC-MS signature result, SWOG Statistics and Data Management Center will provide instructions for resubmission
* STEP 1 SCREENING REGISTRATION: NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* STEP 1 SCREENING REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. Documentation of informed consent via remote consent is allowed
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2 RANDOMIZATION: NOTE: Participants must be registered to step 2 randomization within 70 days after registration to step 1. Participants must plan to start protocol therapy no more than 14 days after step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have castrate levels of testosterone with a baseline level \< 50ng/dL within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have evidence for metastatic prostate cancer by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). Visceral and/or soft-tissue metastases must be ≥ 1.0 cm in diameter and lymph nodes must be \> 1.5 cm diameter in the short axis. Scans must be obtained within 28 days prior to randomization
* NOTE: All disease must be assessed and documented on the baseline/pre-registration tumor assessment form
* STEP 2 RANDOMZIATION: Participants must have progressive disease (PD) in the opinion of the treating investigator according to any of the following criteria
* Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable disease must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) \[CT scan thickness no greater than 5 mm\] or magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. Previously irradiated lesions, primary prostate lesion and bone lesions will be considered non-measurable disease
* Progression in bone as evidenced by:
* Appearance of 2 or more new bone lesions on bone scan (BS). If equivocal, they must be confirmed by other imaging modalities (CT; MRI), and/or repeat BS \> 4 weeks later
* Appearance of a new lytic lesion(s) and/or increasing size of an existing lesion by CT/MRI, since AVPC tumors may produce lytic bone lesions that are not detected on conventional bone scans
* Rising prostate-specific antigen (PSA) defined (Prostate Cancer Working Group 2 \[PCWG2\]) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. In case of progression based on rising PSA only, the first rising PSA (measure 2) must be obtained within 6 months of initiation of androgen receptor (AR) targeted therapy (≤ 6 months)
* Clinical progression. Increasing symptoms unequivocally attributed to disease progression as judged by the treating physician
* STEP 2 RANDOMIZATION: Participants must not have received prior cabazitaxel or carboplatin
* STEP 2 RANDOMIZATION: Participants must not be receiving treatment on another therapeutic clinical trial at the time of randomization. Chemotherapies, bone targeting therapies, immunotherapies and clinical trial agents must be discontinued ≥ 21 days prior to randomization. Stereotactic radiation (SART) must be discontinued ≥ 3 days prior to randomization
* STEP 2 RANDOMIZATION: Participants must not be receiving radiation therapy or kyphoplasty-vertebroplasty within 14 days prior to randomization or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must not have untreated fractures and/or cord compression
* STEP 2 RANDOMIZATION: Participants must not have symptomatic uncontrolled brain metastases. Properly treated brain metastases (i.e., with stereotactic radiation) within 14 days are allowed
* STEP 2 RANDOMIZATION: Participants must have Zubrod performance status of 0 - 2 within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have a complete medical history and physical exam within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Platelets ≥ 100 x 10\^3/uL (unless clinical evidence of bone marrow infiltration by tumor in which case \> 75 x 10\^3/uL are allowed) (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Total bilirubin ≤ institutional upper limit of normal (ULN) with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome or if the participant has liver metastases and/or acute tumor associated illness \< 4x ULN (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (or if participant has liver metastases and/or acute tumor-associated illness, ≤ 4x institutional ULN) (within 28 days prior to step 2 randomization)
* STEP 2 REGISTRATION: Participants must have a calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants with peripheral neuropathy must have ≤ grade 2 peripheral neuropathy (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Participants who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including vasectomy with testing showing no sperm in the semen
* STEP 2 RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen
* STEP 2 RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* STEP 2 RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabazitaxel, DRUG: Carboplatin, PROCEDURE: Chest Radiography, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, DRUG: Prednisone
Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation (ReSPECT)
Head of Clinical Operations - terry.nichols@mundipharma-rd.eu
NCT04368559
Inclusion Criteria:
• Willing and able to provide written informed consent.
• Males or females ≥18 years of age.
• Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
• Diagnosed with 1 of the following underlying diseases:
• Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
• Acute lymphoblastic leukemia, in first or second complete remission.
• Acute undifferentiated leukemia in first or second remission.
• Acute biphenotypic leukemia in first or second complete remission.
• Chronic myelogenous leukemia in either chronic or accelerated phase.
• One of the following myelodysplastic syndrome(s) defined by the following: i. Refractory anemia. ii. Refractory anemia with ringed sideroblasts. iii. Refractory cytopenia with multilineage dysplasia. iv. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts. v. Refractory anemia with excess blasts - 1 (5-10% blasts). vi. Refractory anemia with excess blasts - 2 (10-20% blasts). vii. Myelodysplastic syndrome, unclassified. viii. Myelodysplastic syndrome associated with isolated del (5q). g. Lymphoma (including Hodgkin's) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related or unrelated donor transplant. h. Aplastic anemia. i. Primary or secondary myelofibrosis. j. Chronic myelomonocytic leukemia. k. Chronic lymphocytic leukemia. l. Drepanocytosis (sickle cell anemia). m. Red blood cell aplasia. n. Myeloproliferative disorder, unclassified. o. Multiple myeloma (plasma cell myeloma).
• Receiving myeloablative or reduced-intensity conditioning regimens.
• Adequate renal and hepatic function prior to initiation of conditioning regimen, therefore between 40 days prior and 10 days prior to BMT, documented as follows:
• Hepatic: alanine aminotransferase less than or equal to (≤) 2.5 × upper limit of normal (ULN) and total serum bilirubin ≤1.5 × ULN (excluding Gilbert's Syndrome).
• Renal: serum creatinine ≤2 milligrams (mg)/deciliter (dL) and with creatinine clearance (CrCl) greater than or equal to (≥) 30 milliliters (mL)/minute (min) without a history of renal transplant, or undergoing weekly dialysis within 4 weeks of the BMT.
• Baseline blood samples drawn for Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 15 days before randomization, with results available prior to randomization.
• Baseline Toxoplasma serologies available within 6 weeks prior to randomization. Subjects with a positive toxoplasma IgG serology at any time prior to randomization do not need to repeat the toxoplasma serologies (IgG and IgM) and will be considered to have a prior history of toxoplasmosis.
• Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency determination by the investigator prior to randomization with no known evidence of G6PD deficiency performed any time prior to randomization. If the Investigator assesses the subject as G6PD sufficient, the G6PD test result does not need to be entered into the EDC system.
• Female subjects of child-bearing potential \<2 years post-menopausal (unless surgically sterile) must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence (only possible if it corresponds to the subject's usual lifestyle) while participating in this study, and for 30 days after the last dose of study drug. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.
Exclusion Criteria:
• Diagnosis of AML not in morphological remission.
• Diagnosis of chemotherapy-resistant lymphoma: a first relapse can occur provided that a second complete remission has occurred.
• Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of randomisation.
• Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤50%, or shortening fraction ≤26%.
• Personal or family history of Long QT interval on electrocardiogram (ECG) (QT) syndrome or a prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) (\>470 milliseconds \[msec\] in males and \>480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, quinidine, or halofantrine.
• Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin) or forced expiratory volume in 1 second (FEV1) ≤65% of predicted value, or O2 saturation ≤82% on room air.
• Suspected or documented PCP within 2 years of screening.
• Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (Fungitell ≥80 picograms \[pg\]/mL or Fujifilm Wako \>11 pg/mL) within 15 days prior to the transplant.
• Receipt of previous allogeneic BMT.
• Planned receipt of cord blood for transplantation.
• Planned peripheral blood or marrow autograft.
• Not applicable to protocol Amendment 6.
• Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• History of severe (Grade ≥3) ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
• . .
• Planned or ongoing intake at screening of a known severe neurotoxic medication or with a known moderate neurotoxic medication in a patient with ataxia, tremor, motor neuropathy, or sensory neuropathy of CTCAE version 5.0 Grade 1 or higher.
• Any contraindication or a medication or supplement known to severely interact with the standard antimicrobial regimen (SAR) as detailed in the US Prescribing Information (USPI) or Summary of Product Characteristics (SmPC) of fluconazole, posaconazole, or TMP/SMX.
• Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
• Known hypersensitivity or inability to receive TMP/SMX or any of its excipients, including but not limited to anaphylaxis, exfoliative skin disorders, or acute porphyria.
• Recent use of an investigational medicinal product within 28 days or 5 half-lives of the investigational medicinal product, whichever is greater, to prevent overlapping toxicities when this study's investigational product is dosed, or presence of an investigational device at the time of screening. In some cases, use of investigational products may be acceptable in consultation with the Sponsor's Medical Monitor.
• Known infection with HIV. Subjects with unknown HIV status should be tested for HIV antibodies per standard of care.
• Pregnant or lactating females.
• The Principal Investigator (PI) determines that the subject should not participate in the study.
• Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).
• Known liver cirrhosis, diagnosed according to country or Medical Society specific guidelines and documented in the medical records prior to initiating conditioning regimen.
DRUG: Rezafungin for Injection, DRUG: Posaconazole, DRUG: Fluconazole, DRUG: Trimethoprim-sulfamethoxazole (TMP/SMX), DRUG: Intravenous Placebo, DRUG: Oral Placebo
Candidemia, Mycoses, Fungal Infection, Fungemia, Invasive Candidiasis, Pneumocystis, Mold Infection, Invasive Fungal Disease, Prophylaxis of Invasive Fungal Infections, Aspergillus
Mycoses, Prophylaxis of Invasive Fungal Infections, Aspergillus, Candidiasis, Candidemia, Candidiasis, Invasive, Fungemia, Sepsis, Blood and Marrow Transplant (BMT), Infection, Invasive Fungal Infections, Systemic Inflammatory Response Syndrome, Inflammation, Pathologic Processes, Fluconazole, Posaconazole, Caspofungin, Trimethoprim-sulfamethoxazole (TMP/SMX), Echinocandins, Antifungal Agents, 14-alpha Demethylase Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Steroid Synthesis Inhibitors, Physiological Effects of Drugs, Cytochrome P-450 CYP2C9 Inhibitors, Cytochrome P-450 CYP2C19 Inhibitors, Pneumocystis, Mold Infection, Rezafungin, Anti-Infective Agents
A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
Medical Affairs at AskBio - AskFirst@askbio.com
NCT05230459
Inclusion Criteria:
• Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
• Ability to ascend 4 stairs between 2.5 and 10 seconds.
• Ability to walk/run 10 meters in \<30 seconds.
• Able to understand and comply with all study procedures.
• Sexually active females of childbearing potential and female and male partners of male subjects receiving study intervention must use a barrier method of contraception for the first 6 months after dosing.
Exclusion Criteria:
• Significant cardiomyopathy as defined by echocardiogram (left ventricular ejection fraction \<40%), evidence of conduction defect (increased PR and RR intervals, left bundle branch block and QTcF \>480m/sec), NYHA Class 3 or 4 heart failure, or MRI gadolinium enhancement evidence of clinically important myocardial fibrosis.
• Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
• Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
• History of active, ongoing chronic liver disease (e.g. hepatitis, HIV-related liver disease, hemochromatosis, steatosis, etc.) or abnormal liver function tests (abnormal GGT and/or abnormal total/direct bilirubin \>upper limit of normal \[ULN\] and/or elevated AST and ALT \>2 ULN).
• Abnormal renal function (GFR \<60 ml/min, using the Modification of Diet in Renal Disease equation).
• Any life-threatening disease, including malignant neoplasms and medical history or malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
• In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
• Requirement for daytime ventilatory support.
• Change in glucocorticosteroid treatment within 3 months prior to screening visit.
• Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
• Ongoing participation in any other therapeutic clinical trial.
• Neutralizing antibody titer to AAV9 \>1:5.
• Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.
GENETIC: AB-1003 dose level 1, GENETIC: AB-1003 dose level 2, OTHER: Placebo
Limb Girdle Muscular Dystrophy, Limb-Girdle Muscular Dystrophy Type 2, LGMD2I, Muscular Dystrophy, LGMD2, LGMD, FKRP, FKRP Mutation, Fukutin Related Protein
gene therapy, LGMD2I, LGMD2I/R9, gene augmentation therapy, FKRP, fukutin related protein, FKRP mutation
Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma (STRASS2)
EORTC HQ - 1809@eortc.org
NCT04031677
• STRASS 2
Inclusion Criteria:
* Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
* LMS:
* Any grade LMS can be included
* Minimum size of LMS tumor should be 5 cm
* LPS:
* Diagnosis should be confirmed based on MDM2 (Mouse double minute 2 homolog) and CDK4 (Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while proof of MDM2 amplification is highly recommended.
* All grade 3 DDLPS can be included.
* DDLPS with confirmed grade 2 on biopsy can be included when:
* The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy).
* The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
* Unifocal tumour
* Resectable tumour: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcoma team. A patient is not considered resectable when the expectation is that only an R2 resection is feasible.
* Criteria for non-resectability are:
* Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein
* Involvement of bone
* Growth into the spinal canal
* Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium
* Infiltration of multiple major organs like liver, pancreas and or major vessels
* Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. CT thorax abdomen pelvis with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen \& pelvis
* Collection of tumour tissue for central pathology review is mandatory.
* For patients with LMS: if there is not enough tissue for assessing the grading, this is acceptable.
* If tumour tissue is not available for the central pathology review, patient will not be eligible.
* If the biopsy was not done or the FFPE of the biopsy not available but at least 10 unstained slides or one pathological block are available for the central review, that will be considered as acceptable.
* For the biopsy if fine needle aspiration (FNA) is performed instead of core needle biopsy (CNB) recommended by the standard guidelines, please contact the EORTC medical monitors for further evaluation.
* Collection of tumour tissue and blood samples for translational research is mandatory.
* In case there is not enough tissue for TR, a new biopsy is not required and if the patient fulfils all other eligibility criteria, he/she will be eligible.
* If the blood samples are not collected, patient will not be eligible.
* If the patient refuses the collection of biomaterial for TR, patient will not be eligible even if he/she fulfils all other eligibility criteria
* ≥ 18 years old (no upper age limit)
* WHO performance status ≤ 2
* Adequate haematological and organ function
* American Society of Anaesthesiologist (ASA) score \< 3
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
Note: a woman is considered of childbearing potential, i.e., fertile, if she is following menarche. She remains of childbearing potential until she becomes post-menopausal or permanently sterile.Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 consecutive months without menses, a single FSH measurement is insufficient.
* WOCBP in both arms should use highly effective birth control measures, during the study treatment period and for at least 6 months after the last dose of chemotherapy or date of surgery (except for women receiving chemotherapy with ifosfamide who should continue contraception until 1 year after last day of treatment). A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
* For men in the experimental arm: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
* Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6months after the last study treatment.
* Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria:
* Sarcoma originating from bone structure, abdominal or gynecological viscera
* Extension through the sciatic notch or across the diaphragm
* Metastatic disease
* Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour
* Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
* Congestive heart failure
* Angina pectoris
* Myocardial infarction within 1 year before randomization
* Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy.
Note: in case of high blood pressure: 1) initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 2) blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 150/90mmHg in order for a patient to be eligible for the study.
* Uncontrolled cardiac arrhythmia
* Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Active and uncontrolled infections
* Vaccination with live vaccines within 30 days prior to study entry
* Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
* Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer.
* Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum.
* Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
* Known contraindication to imaging tracer and to MRI
• Selection criteria for STREXIT 2 * Patients with histologically proven primary resectable localized high-risk DDLPS or LMS of retroperitoneal space or infra-peritoneal spaces of pelvis (as described in the inclusion criteria of STRASS 2) and amenable to receive chemotherapy but for whom the list of eligibility criteria for the study is too restrictive (tumour grading not available, inadequate organ function, concomitant diseases) * Patients who meet all eligibility criteria of STRASS 2 but do not consent to randomization or are not enrolled for any other reason. * Patients enrolled in a Registry collecting data on primary RPS patients in the centres participating in STRASS 2 (e.g., RESAR) and who satisfy the above criteria.
• Selection criteria for preferences for neoadjuvant chemotherapy in STRASS 2 substudy All patients recruited to STRASS 2 in participating centres (Australia +/- international sites) that are able to read, comprehend and write in English at a sufficient level to complete study materials.
PROCEDURE: Surgery, DRUG: Preoperative chemotherapy
Retroperitoneal Sarcoma, Liposarcoma, Leiomyosarcoma
Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study
ctrrecruit@vcu.edu
NCT05863351
Inclusion Criteria:
* Patient must be \>= 18 years of age
* Patient must have a pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma (RCC) prior to randomization
* Patient may have any RCC histology except a histology that has a sarcomatoid component
* Patient must have primary site addressed by local therapy. If the primary RCC is intact, the patient must undergo local treatment to the primary before randomization
* Patient must have favorable or intermediate International Metastatic RCC Database Consortium (IMDC) risk (0-2) at the time of randomization
* Patient must have a total of between 2 and 5 metastatic lesions, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with imaging obtained within 45 days prior to randomization
* Patient must have a documentation from a radiation oncologist confirming that all sites are amenable to SAbR
* Patient may have received prior therapy in the adjuvant setting as long as potential trial participants have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point
* Has not undergone a hysterectomy or bilateral oophorectomy
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must have a Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Patients must have adequate organ and bone marrow function as per the recommended guidelines and the respective Food and Drug Administration \[FDA\] package insert required for the systemic therapy chosen by the treating oncologist. We recognize that patients may have varying levels of renal and liver function that will impact which systemic therapy is appropriate for the patient. We do not require all patients to have specific baseline laboratory thresholds but do ask the treating oncologist to attest that the patient has adequate organ and bone marrow function to safely receive one of the first line systemic therapies listed in the protocol as a standard of care treatment option
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study
* For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study
* In order to participate in the QOL portion of the protocol, the patient must speak one of the languages in which the NFKSI-19 and EQ-5D-5L is available
* NOTE: Sites cannot translate the associated QOL forms
Exclusion Criteria:
* Patient must not have brain metastases
* Patient must not have metastasis involving the following locations: ultra-central (within 2cm of carina) lung, invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum), skin, and scalp
* Patient must not have received any prior systemic therapy (except for adjuvant setting) for metastatic RCC
* Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
* Active tuberculosis (purified protein derivative \[PPD\] response without active TB is allowed)
* Uncontrolled hypertension (systolic blood pressure \[BP\] \> 190mmHg or diastolic BP \> 110mmHg)
* Major surgery within 30 days prior to randomization
* Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization
* Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-STEMI \[NSTEMI\], cerebrovascular accident \[CVA\], etc.) events within 180 days prior to randomization
* Moderate or severe hepatic impairment (child-Pugh B or C)
* Untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed. Treated PE or DVT is allowed \> 30 days from diagnosis and when not resulting in respiratory impairment
* Unstable cardiac arrhythmia within 180 days prior to randomization
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization
* History of or active inflammatory bowel disease
* Malabsorption syndrome within 30 days prior to randomization
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, PROCEDURE: Stereotactic Ablative Radiotherapy, PROCEDURE: Systemic Therapy
Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8
Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Erin Rogers - erogers@swog.org
NCT05633615
Inclusion Criteria:
* STEP 1: REGISTRATION: Participants must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma or follicular lymphoma grade 3b or primary mediastinal large B-cell lymphoma (PMBCL)
* STEP 1: REGISTRATION: Participants with transformed DLBCL must have transformed DLBCL from follicular or marginal zone lymphoma
* STEP 1: REGISTRATION: Participant must have bi-dimensionally measurable systemic disease (at least one lesion with longest diameter \> 1.5 cm)
* STEP 1: REGISTRATION: Participants with secondary central nervous system (CNS) lymphoma (parenchymal, spinal cord, meningeal, cerebrospinal fluid involvement) must be asymptomatic from their CNS disease
* STEP 1: REGISTRATION: Participants must be registered for step 1 after they have signed institutional consent for CAR T-cell leukapheresis but prior to the start of lymphodepleting (LD) chemotherapy for commercial CAR T-cell product
* STEP 1: REGISTRATION: In the opinion of the enrolling physician, participants must be felt to be a candidate for CAR T-cell therapy with plans to be treated with Food and Drug Administration (FDA) approved commercially available CD19 CAR T-cell construct.
* Participants must qualify for commercially approved CD19 CAR T-cell therapy per FDA package insert.
* If the CAR T-cell product does not meet parameters to be given as an FDA approved product (i.e. does not meet specification criteria mandated by FDA and is infused under an expanded access protocol \[EAP\] or single participant investigational new drug \[IND\]) the participant will be taken off of study and no longer be eligible for step 2 randomization
* STEP 1: REGISTRATION: Participants are permitted to receive or have received 'bridging therapy' after CAR T-cell leukapheresis. However, participants must not receive polatuzumab vedotin, and/or mosunetuzumab as part of bridging therapy.
* Bridging therapy is defined as lymphoma directed therapy administered between leukapheresis and the start of LD chemotherapy. This includes cytotoxic chemotherapy (e.g.: bendamustine and rituximab \[BR\], rituximab, gemcitabine and oxaliplatin \[R-gem/ox\]), radiation, corticosteroids, as well as novel therapies such as BTK inhibitors (e.g.: Ibrutinib), immunomodulators (e.g.: lenalidomide), monoclonal antibodies (e.g.: rituximab, obinutuzumab, tafasitamab) antibody drug conjugates (e.g: loncastuximab), checkpoint inhibitors (e.g.: pembrolizumab, nivolumab), clinical trial treatments, etc.
* If a participant receives polatuzumab vedotin or mosunetuzumab as bridging they will ineligible to continue on step 1 registration portion of the study and be ineligible for step 2 randomization
* STEP 1: REGISTRATION: PET-CT scan must be planned for completion within 60 days prior to the start of LD chemotherapy.
* All pre-CAR T-cell therapy disease must be assessed and documented on the baseline/pre-registration tumor assessment form.
* If receiving bridging therapy, participants must have a PET-CT scan upon completion of all planned bridging therapy. If the PET-CT scan after completion of bridging therapy is consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* Participants are permitted to receive corticosteroids after leukapheresis without the need to repeat a PET-CT scan. If steroids are used, they must be planned to stop no later than 3 days before CAR -T cell infusion.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 1: REGISTRATION: Participants that have previously been treated with polatuzumab vedotin or mosunetuzumab prior to CAR T-cell leukapheresis for either indolent or aggressive NHL are eligible as long as the participant did not have refractory disease or progression/relapse within 6 months of the last infusion with either agent
* STEP 1: REGISTRATION: Participants must be planning to receive CAR T-cell infusion no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy. Any participant receiving CAR T-cell infusion outside of this window will be ineligible for step 2 randomization
* STEP 1: REGISTRATION: LD chemotherapy prior to CAR T-cell infusion must be planned to start within 60 days after step 1 registration
* STEP 1: REGISTRATION: Participants must be \>= 18 years of age at the time of registration
* STEP 1: REGISTRATION: Participants must have Zubrod performance score (PS) of 0, 1, or 2
* STEP 1: REGISTRATION: Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 1: REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 14 days prior to registration)
* STEP 1: REGISTRATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 14 days prior to registration. Estimated creatinine clearance is based on actual body weight
* STEP 1: REGISTRATION: Participants must have an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 60 days prior to registration with a cardiac ejection fraction \>= 40%.
* Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
* Participants must not have documented myocardial infarction and percutaneous coronary intervention (PCI) within 6 months prior to registration or myocardial infarction without PCI within 3 months of registration, or unstable angina
* STEP 1: REGISTRATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 1: REGISTRATION: Participants with hepatitis B virus infection must have undetectable viral load within 14 days prior to registration, be on suppressive therapy and have no evidence of hepatitis B virus (HBV) related hepatic damage
* STEP 1: REGISTRATION: Participants with hepatitis C infection must have eradication therapy completed, have no evidence of hepatitis C infection (HCV) related damage and have undetectable viral load within 14 days prior to registration
* STEP 1: REGISTRATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* STEP 1: REGISTRATION: Participants must be offered the opportunity to participate in banking for planned translational medicine and future research. With participant consent, any residuals from the mandatory tissue submission will also be banked for future research.
* Note: Streck tubes must be ordered in advance. Please allow 5-7 days for shipment of the collection kits
* STEP 1: REGISTRATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for step 1 registration
* STEP 2: RANDOMIZATION: Participant's CAR T-cell product must have met specification parameters to be given as an FDA approved commercial product
* STEP 2: RANDOMIZATION: Participants must have a PET-CT scan between days 25-40 after CAR T-cell infusion and determined to have a response consistent with stable disease or partial remission by central review compared to most recent pre-LD chemo/CAR T-cell PET-CT scan.
* Note: Patients with delayed enrollment \> 21 days after 'day +30' PET-CT scan will necessitate a repeat PET-CT scan if concerning signs or symptoms of lymphoma progression develop.
* Note: If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Eligible participants must be randomized no later than 60 days after CAR -T infusion
* STEP 2: RANDOMIZATION: Participants must have started LD chemotherapy within 60 days of signing consent for step 1 registration
* STEP 2: RANDOMIZATION: Participants must have S2114 CAR T-cell therapy form submitted to Southwest Oncology Group (SWOG) prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants must have had a PET-CT scan upon completion of all planned bridging therapy if received, with the exception of up to 7 days of corticosteroids. If the PET-CT scan after completion of bridging therapy was consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Participants must have Zubrod PS of 0, 1, or 2
* STEP 2: RANDOMIZATION: Absolute neutrophil count (ANC) \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Total bilirubin =\< 2 x institutional ULN (within 7 days prior to step 2 randomization)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 2: RANDOMIZATION: AST and ALT =\< 3 x institutional ULN (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 7 days prior to step 2 randomization. Estimated creatinine clearance is based on actual body weight (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 2: RANDOMIZATION: Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 2: RANDOMIZATION: Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 2 randomization and on suppressive therapy
* STEP 2: RANDOMIZATION: Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be continuing to receive anti-retroviral therapy and have an undetectable viral load test within 14 days prior to step 2 randomization
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have documented disease progression while on Arm 4 (observation) on this protocol. The follow-up tumor assessment form documenting disease progression must be submitted to SWOG prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must be registered within 28 days of the date of progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have imaging that clearly demonstrates progression compared to day +30 PET-CT scan
* Note: These scans should be performed as standard of care and only performed between scheduled response assessments required for study if symptoms arise that are concerning for progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have Zubrod PS of 0, 1, or 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): ANC \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Total bilirubin =\< 2 x institutional ULN (within 14 days prior to step 3 crossover registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): AST and ALT =\< 3 x institutional ULN
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within days prior to step 3 crossover registration. Estimated creatinine clearance is based on actual body weight (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with peripheral neuropathy must have \< grade 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration and on suppressive therapy
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with known human immunodefici BIOLOGICAL: Axicabtagene Ciloleucel, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Fludarabine, BIOLOGICAL: Lisocabtagene Maraleucel, BIOLOGICAL: Mosunetuzumab, OTHER: Patient Observation, DRUG: Polatuzumab Vedotin, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tisagenlecleucel
Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma, Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Transformed Follic Lymph to Diff Large B-Cell Lymphoma, Transformed Marg Zone Lymph to Diff Large B-Cell Lymphoma
Evaluating the Impact of Social and Genetic Factors on Outcomes in Adolescent and Young Adult Cancer Survivors
ctrrecruit@vcu.edu
NCT06002828
Inclusion Criteria:
* Patient must be \>= 18 years of age at the time of registration
* Patient must have been between the ages of 15-39 at the time of their first primary cancer diagnosis of Hodgkin lymphoma or non-Hodgkin lymphoma (NHL)
* Patient must have completed therapy (with a complete response, per clinician determination) at the time of registration
* Patients last date of prior systemic therapy for first primary diagnosis for Hodgkin lymphoma or non-Hodgkin lymphoma must have been within one year prior to registration
* NOTE: Systemic therapy refers to all anti-cancer therapy, including but not limited to chemotherapy, intravenous (IV) or oral targeted medications, or radiation, and administered via a clinical trial or standard approach
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3
* Patient must be English speaking in order to be able to complete the required QOL forms on this study
* NOTE: Sites cannot translate the associated QOL forms
* Patient must not be receiving active therapy for Hodgkin lymphoma or non-Hodgkin lymphoma
* Patient must have internet access through computer, tablet, or smartphone
* Patient must have email address
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible PROCEDURE: Biospecimen Collection, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma, Non-Hodgkin Lymphoma
ULTRA-HFIB-Redo: Ultrasound-based Renal Sympathetic Denervation Vs Control in Redo Ablation Patients
Jeff Lam, MS - jeff.lam@mountsinai.org
NCT05988411
Inclusion Criteria:
* Age ≥ 18;
* Planned for a redo AF ablation procedure (paroxysmal or persistent); (prior to randomization, a technically successful AF ablation procedure, defined as successful pulmonary vein isolation, if needed, as well as bidirectional block of any attempted anatomic lesion sets such as cavotricuspid isthmus line, roofline, mitral line and superior vena cava isolation, must have been completed). Note: the clinical recurrences must primarily be atrial fibrillation, and not atrial flutter/tachycardia (that is, a prospective patient may have a AFL/AT recurrences, but AF must be the dominant recurrent rhythm.)
* History of hypertension and either:
* Documented history of SBP≥160 or DBP≥100, or;
* Receiving ≥1 antihypertensive medication;
* Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements
Exclusion Criteria:
* Long-standing persistent AF (\>12 months); \>3 prior atrial fibrillation ablations (lifetime); AF ablation within 3 months of enrollment; extensive scar in left atrium.
* Individual with valvular AF or AF due to a reversible cause
* Prior treatment with other devices for hypertension including but not limited to ROX Coupler, Mobius stent, and/or the CVRx barostimulator device.
* NYHA class IV congestive heart failure;
* Individual has renal artery anatomy that is ineligible for treatment (as determined by renal angiography);
* Main renal artery diameter \<3mm or \>8.0 mm
* Main renal treatable artery length \< 20 mm (length may include proximal branches)
* Presence of renal artery stenosis of any origin ≥30%
* Calcification in renal arteries
* Prior renal denervation procedure
* Presence of abnormal kidney tumors
* Renal artery aneurysm
* Pre-existing renal stent or history of renal artery angioplasty
* Pre-existing aortic stent or history of aortic aneurysm
* Fibromuscular disease of the renal arteries
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Individual has an estimated glomerular filtration rate (eGFR) of less than 40mL/min/1.73m2, using the MDRD calculation;
* Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus, contraindication to all anticoagulation)
* Individual with known allergy to contrast medium not amendable to treatment.
* Life expectancy \<1 year for any medical condition
* Individual has experienced a myocardial infarction, unstable angina, cerebrovascular accident, or heart failure admission within 3 months of the baseline visit.
* Documented history of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis.
* Female participants who are pregnant or nursing.
* Individual has known secondary hypertension.
* Individual has a single functioning kidney (either congenitally or iatrogenically).
* Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
* Patients concurrently enrolled in any other investigational drug or device trial that would interfere with the conduction of this protocol. DEVICE: Renal Denervation, DEVICE: Catheter Ablation
Paroxysmal Atrial Fibrillation, Persistent Atrial Fibrillation
Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial
ctrrecruit@vcu.edu
NCT05710328
Inclusion Criteria:
* Patients (all genders) must be \>= 18 years of age.
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines that has been determined by local testing.
* Patient must have known (either positive or negative) hormone receptor (estrogen receptor \[ER\] or progesterone receptor \[PR\]) status by local testing, per ASCO/CAP guidelines. Patients with either hormone receptor-positive or hormone receptor- negative HER2-positive breast cancer are eligible.
* Patient must have American Joint Committee on Cancer (AJCC) 8th Edition stage IIa-IIIc according to anatomic staging table at diagnosis and below criteria.
* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-4)
* Patients with nodal involvement (cN1-3) are eligible if T2-4
* Patients with clinical T4d are not eligible
* Patients with bilateral invasive breast cancers are eligible if both cancers are HER2-positive and at least one meets all protocol eligibility criteria and neither cancer renders the patient ineligible.
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive and at least one tumor focus meets all eligibility criteria. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing.
* Patient must plan to start a standard neoadjuvant pertuzumab (or other biosimilars) based regimen.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of this imaging intervention are eligible for this trial.
* Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
* Patient must be participating in the trial at an institution which has agreed to perform the imaging research studies, completed the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Center Group (ECOG-ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval.
* For patients who completed the baseline (T0) FDG-PET/CT PRIOR to registration, neoadjuvant pertuzumab-based regimen must start after study registration and within 21 days after the T0 scan.
* Patients must not have used colony stimulating growth factors within 14 days prior to completing a T0 scan done prior to registration.
Exclusion Criteria:
* Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy.
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the teratogenic effects of FDG in addition to the radiation exposure during PET/CT. All patients of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy.
* NOTE: A pregnancy test within 7 days prior to the T0 scan is also required but will only need to be done if a) the T0 scan is completed after study registration and b) if the pregnancy test done prior to registration is completed outside of the 7-day window.
A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patient must not have any contraindication to FDG-PET/CT imaging which includes routine glucose values \> 200 mg/dL and severe claustrophobia. DRUG: Chemotherapy, PROCEDURE: Computed Tomography, OTHER: Fludeoxyglucose F-18, PROCEDURE: Positron Emission Tomography, PROCEDURE: Surgical Procedure
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2-Positive Breast Carcinoma, Invasive Breast Carcinoma
EPPIC-Net: Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy
Neha Rupeja - nrupeja@mgh.harvard.edu
NCT05476276
• 1. Platform Protocol Inclusion Criteria (To be used in conjunction with ISA-specific criteria. Note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility.) Participants must meet all of the following inclusion criteria:
• Able to provide informed consent. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants.
• 18 years of age and older
• Diagnosis of diabetes mellitus
• Meets the Toronto Criteria for probable clinical sensorimotor polyneuropathy, with PDPN symptoms present for at least six months. This is defined as a combination of symptoms and signs with any two or more of the following (must be present bilaterally in the distal lower extremities): neuropathic symptoms, decreased distal sensation, or unequivocally decreased (or absent) ankle reflexes. Specifically:
• The presence of any neuropathic symptoms on either the "Douleur Neuropathique en 4 Questions" (DN4) or the EPPIC-Net Neuropathy Exam will suffice to demonstrate "neuropathic symptoms."
• Decreased distal sensation is satisfied by any of the following: i. "Yes" is checked at least once under Question 3 of the DN4 which queries hypoesthesia to touch and pinprick. ii. At least one score of "reduced" or "absent" on the right AND at least one score of "reduced" or "absent" on the left in any of the following items from the EPPIC-Net Neuropathy Exam: * Pin sensation in segments 1 or 2 (i.e. the toes and feet) * Vibration at the great toe * Joint position at the great toe * Light touch/touch pressure at the great toe * Temperature at the great toe * Monofilament at the great toe c. Decreased or absent ankle reflexes is satisfied by a score of "reduced" or "absent" on the right AND left in the "Ankle reflex" item in the EPPIC-Net Neuropathy Exam.
• A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4).
• Pain reporting during a pre-defined 7-day screening period meets study criteria (to be established using a centrally-administered screening algorithm) which may account for mean pain intensity reported, variability in reported values, and adherence in reporting.
• Patient reported daily 11-point NRS (for average and worst pain over the last 24 hours) is completed on at least 5 out of the 7 days in the screening and baseline periods.
• Participants must be willing and able to comply with scheduled visits, the treatment schedule, laboratory testing, and other requirements of the study (e.g., completion of app-based daily reporting).
• Females may be included if they meet at least one of the following criteria (note that individual ISAs may specify more stringent measures to prevent pregnancy): a. Are not of childbearing potential, defined as one or more of the following: i. Post-menopausal for at least 1 year ii. Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) iii. XY genotype iv. Turner syndrome v. Uterine agenesis. b. Are completely abstinent from sexual activity capable of resulting in pregnancy (as part of their preferred and usual lifestyle). This will include females whose sole sexual partner is a male who has undergone surgical sterilization or vasectomy. c. Women of childbearing potential will agree to practice an effective form of two types of birth control, which are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. This must be done before, throughout, and for 30 days after the last dose of DB study drug. Acceptable methods are: i. Hormonal methods such as the vaginal ring, or oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before study drug administration. ii. Intrauterine device. iii. Barrier method of contraception: condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicide
• Specific requirements of male participants (regarding contraception) will be defined in the ISAs based on the potential toxicity profile of the asset.
• 2. Platform Protocol Exclusion Criteria (To be used in conjunction with ISA-specific criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility) Please note that some of the below criteria which depend on clinical judgment require contacting the MM. Participants must not meet any of the following exclusion criteria, organized by category:
• 2.1. Neuropathy Confound Exclusion Criteria
• Peripheral neuropathy that is known to have been caused by a condition other than diabetes (e.g. HIV, cancer/chemotherapy-induced, other medication-induced, alcohol-induced, hereditary, autoimmune neuropathies, uncontrolled or untreated hypothyroidism). Note that participants will not be tested for HIV, this will be established by patient report or review of the medical record.
• Other significant pain conditions involving the same area as the neuropathy (e.g. physical deformity of the feet, plantar fasciitis, lumbosacral radiculopathy with distal lower extremity pain, fibromyalgia involving the lower limbs, Morton's neuroma), that in the opinion of the investigator would interfere with the participant's ability to rate the neuropathy pain.
• Other pain conditions not involving the same area as the neuropathy which (in the opinion of the investigator) interfere with the participant's ability to rate the neuropathy pain.
• Any amputation of the lower limb which interferes with the participant's ability to rate the neuropathy pain. If there is any amputation please contact the MM to confirm eligibility prior to randomization to an ISA.
• The presence of any current foot ulcer.
• Significant peripheral vascular disease defined as symptoms consistent with intermittent claudication.
• 2.2. Medication/Treatment Exclusion Criteria
• Use of other investigational drugs within 3 months before screening and throughout the study.
• Known or suspected hypersensitivity to all of the assets (active component and excipients) currently being tested in the Platform Protocol.
• Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating device for neuropathic pain in the distal lower limbs within 3 months of screening.
• Use of the high dose capsaicin patch (8%) in the 6 months before screening and throughout the study (for the treatment of PDPN). Use of the capsaicin patch in a manner that is not expected to interfere with the measurement of PDPN severity is allowed.
• Participants who meet any of the following regarding concomitant treatments:
• Unwilling or unable to discontinue episodic or periodic treatments for pain in the distal legs and/or feet (e.g., injections of local anesthetics).
• Starting a new non-pharmacological pain treatment (e.g. relaxation/hypnosis, physical or occupational therapy, any exercise-based therapy, any talk-based therapy, acupuncture, TENS) for the treatment of PDPN within 4 weeks prior to screening OR planning on starting a new non-pharmacologic treatment for PDPN OR planned changes to a stable non-pharmacologic treatment for PDPN during the study. i. Non-pharmacological treatment for conditions other than PDPN is allowed without restriction.
• Active use of opioids or marijuana for any reason at screening and unwilling or unable to discontinue use.
• 2.3. Medical Exclusion Criteria
• Clinically significant ECG or laboratory abnormalities at the Screening Visit that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). Screening ECG and lab results may be repeated without requiring a rescreen, as long as the participant is still within the screening window.
• Participants whose glycemic control has been unstable within 3 months before screening (e.g. ketoacidosis requiring hospitalization).
• Proliferative retinopathy or maculopathy requiring acute treatment.
• Requiring dialysis.
• Myocardial infarction or stroke in the past 6 months.
• Known diagnosis of moderate to severe hepatic impairment (equivalent to Child-Pugh class B or C) OR aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal during the screening process.
• A clinically significant illness or operative procedure within 4 weeks of screening.
• Clinically significant surgery planned during the study period. If a surgery is planned, please contact the MM for approval before randomization.
• History of malignancy or other medical condition that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator).
• Pregnant or nursing. 3.2.4. Psychosocial and Substance Use Disorders Exclusion Criteria
• A clinically significant psychiatric disease that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator).
• Alcohol use disorder or other substance use disorders (other than nicotine or caffeine) in accordance with DSM-5 criteria within 12 months of screening.
• Positive urine drug tests defined as one or more of the following (see Urine Drug Testing Section 6.2.13.5.1):
• Two positive urine drug tests for a prescribed opioid (buprenorphine, opiates, methadone and/or oxycodone), prior to the initiation of investigational product (IP);
• Two positive urine drug tests for marijuana (prescribed or recreational), prior to the initiation of investigational product (IP);
• One positive urine drug test for cocaine, ecstasy, methamphetamines, or phencyclidine (PCP);
• One positive urine drug test for non-prescribed amphetamines, barbiturates, benzodiazepines, or opioids (buprenorphine, opiates, methadone and/or oxycodone).
• Vulnerable persons defined as either of the following:
• Individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Individuals whose judgment has been impaired by their physical, mental, or socio-economical condition and those incapable of giving informed consent.
DRUG: ISA specific
Painful Diabetic Neuropathy
Registry of Avance® Nerve Graft's Utilization and Recovery Outcomes Post Peripheral Nerve Reconstruction (RANGER®)
Stacy Arnold - clinicalresearch@axogeninc.com
NCT01526681
Primary Study Criteria (RANGER Avance):
Inclusion Criteria:
* Males and Females who have undergone nerve repair using the Avance® Nerve Graft for the repair of a nerve injury
* Returned for at least one post-operative follow-up visit
Exclusion Criteria:
• Subject who in the opinion of the investigator, have not or likely will not complete at least some portion of the investigator's recommended follow-up.
Addendum 1 (MATCH) Criteria:
Inclusion Criteria:
* Have nerve transection injuries to the upper extremity;
* Have undergone tension free end to end nerve coaptation on both the proximal and distal portion of the nerve gap with nerve autograft or nerve entubulation with nerve tube conduit at a participating ANG-CP-005 registry site after 2004 and;
* Have completed sufficient follow-up assessments at a regeneration rate of 2mm/day to determine the outcomes of the repair or is willing to comply with site specific post-operative care procedures and assessments to determine the outcome of the repair.
Exclusion Criteria:
* Direct nerve repairs;
* Nerve gaps greater than 70mm;
* Subjects who, in the opinion of the investigator, were non-compliant to the investigator's post-operative treatment or rehabilitation instructions;
* Any subject who at the discretion of the Investigator is not suitable for inclusion in the study.
Addendum 2 (Sensation-NOW) Criteria:
Inclusion Criteria:
* Female ≥ 18 years old
* Undergo post mastectomy autologous breast reconstruction with one type of autologous flap (no stacked reconstructions or use of implant with autologous flap)
* Neurotization must be completed using a donor nerve from the flap and a recipient nerve from the chest
* Complete Sensory Assessment Testing with Semmes Weinstein Monofilaments (SWMF) and the following Breast-Q Questionnaires 60 - 120 days post-reconstruction:
* Breast-Q Physical Well Being of the Chest
* Breast-Q Satisfaction with Breast
* Breast-Q Physical Well Being of the Abdomen
* Breast-Q Abnormal Breast Sensations
* Breast-Q Impact of Breast Sensation on Quality of Life
* Breast-Q Return of Breast Sensation
* Able to provide informed consent and are willing to comply with post-operative care procedures and assessments
Exclusion Criteria:
* Surgical history of secondary revision surgery for partial or total flap loss
* Bilateral reconstruction with non-uniform treatment (i.e. 1 reconstructed breast is non-neurotized, 1 reconstructed breast is neurotized)
* Currently prescribed medication known to impact nerve regeneration or to cause peripheral neuropathy
* Currently undergoing IV chemotherapy or radiation
* Any subject who at the discretion of the Investigator is not suitable for inclusion in the study or is unlikely to comply with follow-up schedule
Additional Eligibility criteria to Modules
Module 1: Native Skin Reconstructions with and without neurotization.
* Buried flap reconstructions from nipple sparing mastectomy or skin sparing mastectomy OR a breast reconstruction from a skin sparing mastectomy with exposed flap skin in the peri-areolar region.
* Sensory assessments must be completed on ≥ 8 Zones of Native Skin.
* Center zone measurement may be on either Native Skin or Flap Skin.
* All Inner and Outer zone measurements must be on Native Skin.
* De-identified photo of the breast reconstruction with 9 zones identified. OTHER: Processed Human Nerve Graft, OTHER: Standard Treatment, Autogenous Nerve Graft, Direct Suture, etc., OTHER: Autogenous Nerve Graft, DEVICE: Nerve Tube Conduit, PROCEDURE: Autologous Breast Reconstruction with Neurotization, PROCEDURE: Autologous Breast Reconstruction without Neurotization
Peripheral Nerve Injuries
Sensory Nerve, Mixed Nerve, Motor Nerve, Neurotization, Nerve Injury, Peripheral Nerve Injury
Comparing Brief Behavioral Therapy (BBT-CI) and Healthy Eating Education Learning (HEAL) for Cancer-Related Sleep Problems While Receiving Cancer Treatment
Brooke Burgess, MS - URCC_19185@urmc.rochester.edu
NCT04829539
Inclusion Criteria:
* Be at least 18 years of age
* Be diagnosed with cancer (stage I, II, III, or IV) with a life expectancy of at least 12 months
* Be currently receiving any cancer treatment (surgery alone is excluded)
* Report sleep disturbance of 3 or greater on the sleep disturbance question: "Rate your sleep disturbance in the past 2 weeks on a scale from 0-10, 0 is no problems and 10 is having the most severe problems"
* Have a score of 2, 1, or 0 on the Eastern Cooperative Oncology Group (ECOG) performance status scale
* Be able to speak, understand and read English to participate in the study assessments and interventions
Exclusion Criteria:
* Have a clinical diagnosis of obstructive sleep apnea or restless leg syndrome (even if controlled)
* Be engaged in a formal cognitive behavioral therapy for insomnia program presently or in the past 30 days. Use of sleep medications are allowed BEHAVIORAL: Behavioral Intervention, BEHAVIORAL: Behavioral Intervention, OTHER: Electronic Health Record Review, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?
Gisela Chelimsky - Gisela.Chelimsky@vcuhealth.org
NCT06616363
POTS sample
Inclusion Criteria:
* symptomatic ≥ 40 bpm rise in heart rate in the first 10 min of a tilt table study without a drop in blood pressure
* Clinical symptoms of orthostatic intolerance
Exclusion Criteria:
* Pregnant or breastfeeding
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic diseases
* Unstable medical conditions
* Use of narcotics
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
POST INFECTION
Inclusion Criteria:
* acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay
Exclusion Criteria:
* Pregnant or breastfeeding
* Chronic prescriptions, history of POTS or orthostatic symptoms, recent inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other unstable chronic diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
HEALTHY CONTROLS
Inclusion Criteria:
* Apparently healthy with no known chronic illnesses
Exclusion Criteria:
* Pregnant or breastfeeding
* History of POTS or orthostatic symptoms, migraines, fibromyalgia, chronic fatigue, PTSD. Functional gastrointestinal disorders, fainting, dysmenorrhea, or other chronic pain syndrome, inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic unstable diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software BEHAVIORAL: Questionnaires to be competed, BEHAVIORAL: Provide list of medication and lifetime events, BEHAVIORAL: Use phone App to record new life events, DEVICE: Will wear an activity monitor, OTHER: Periodic 24-hour urine sodium check, DIAGNOSTIC_TEST: A fMRI scan, DIAGNOSTIC_TEST: A bedside tilt test will be performed, OTHER: IV placed to collect blood samples, OTHER: Stool Sample
POTS - Postural Orthostatic Tachycardia Syndrome
PAG activation, Cardiovagal Modulation
Heuristic Tool To Improve Symptom Self-Management in Adolescents and Young Adults With Cancer
Grace Hodges - hodgesg@vcu.edu
NCT05958316
Inclusion Criteria:
* Has received at least 1 cycle of cancer treatment and is within 3 months of initial cancer diagnosis
* Receiving regularly scheduled cancer treatment and will be receiving at least three more cycles
* Reports at least 1 symptom related to cancer and/or its treatment
* Able to speak, read, and write English as required for completion of the C-SCAT and study measures
Exclusion Criteria:
\- Cognitive and/or physical inability to complete study measures. BEHAVIORAL: Computerized Symptom Capture Tool (C-SCAT) Intervention, BEHAVIORAL: Usual Care Control
Symptoms and Signs, Cancer, Childhood Cancer
Supportive Care, Symptom Management
Mobile Health for Adherence in Breast Cancer Patients
ctrrecruit@vcu.edu
NCT06112613
Inclusion Criteria:
* NON-PATIENT: Participants must be an oncology healthcare provider (i.e., oncologist, advanced practice provider, or oncology nurse)
* NON-PATIENT: Participants must have taken care of at least one patient randomized to Arm B (CONCURxP) who had less than 85% adherence rate at 12 months as measured by the WiseBag
* NON-PATIENT: Participant must speak English
* NON-PATIENT: Participant must be employed at an National Cancer Institute Community Oncology Research Program (NCORP) site for at least 6 months
* NON-PATIENT: Participant must be able to provide informed consent to participate in this study
* PATIENT STEP 0: Patient must be \>= 18 years of age
* PATIENT STEP 0: Patient must be fluent in written and spoken English OR patient must be fluent in written and spoken Spanish
* PATIENT STEP 0: Patient must present with new or established pathologically proven hormone receptor (HR)+ HER2- metastatic breast cancer at the time of Step 0
* PATIENT STEP 0: Patient must have initiated any of the CKD4/6 inhibitors (palbociclib or Ibrance, ribociclib or Kisqali, abemaciclib or Verzenio) within 30 days prior to consenting to Step 0 or have received a prescription order with stated intent to initiate within 30 days following Step 0 consent
* NOTE: Patients who have been treated previously with anticancer treatments other than CDK4/6 inhibitors are eligible
* NOTE: CDK4/6 inhibitors must be provided/supplied as a single agent blister pack. If the medication is supplied as capsules in a pill bottle (e.g., Ibrance capsules), patient is not eligible
* NOTE: Ribociclib (Kisqali) and abemaciclib (Verzenio) are only available in blister packs. Palbociclib (Ibrance) is the only CDK4/6 inhibitor that might be available in a capsule formulation. However, this is an outdated formulation and is rarely prescribed as a new start. The format of ordered palbociclib can be determined based on the prescription order
* PATIENT STEP 0: Patients must not have been previously treated with any of the following CDK4/6 inhibitors: Palbociclib or Ibrance, ribociclib or Kisqali, and abemaciclib or Verzenio
* PATIENT STEP 0: Patients must not already be enrolled in a therapeutic clinical trial that monitors CDK4/6 inhibitors
* PATIENT STEP 0: Patient must confirm that they intend to receive their care or monitoring at an NCORP site
* PATIENT STEP 0: Patient must have a personal mobile phone in which they are able and willing to send and receive text messages
* NOTE: The restriction to those with mobile phone access with text messaging is based on the primary intention of the study which involves the use of text messaging to improve adherence
* PATIENT STEP 0: Patient must have an email address
* NOTE: The restriction to those with an email address is based on the primary intention of the study which involves patients responding to questions regarding their reasons for non-adherence after every missed dose to improve adherence
* PATIENT STEP 0: Patient must have the ability to understand and the willingness to sign a written informed consent document
* NOTE: Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available are not eligible
* PATIENT STEP 0: Patient must not have an Eastern Cooperative Oncology Group (ECOG) performance status \>= 3 OR patient must not be deemed medically unable to participate in the study by the study investigators or an oncology clinician (i.e., referral to hospice)
* PATIENT STEP 0: Patient must not be enrolled in other trials offering financial assistance
* NOTE: Gift cards for survey completion, parking passes, or free medication provided as part of therapeutic trials are not considered financial assistance
* PATIENT STEP 1: Patient must meet all the eligibility criteria for Step 0
* PATIENT STEP 1: Patient must have signed a written informed consent form
* PATIENT STEP 1: Patient must have completed baseline survey within 30 days of the date of Step 0 Registration
* PATIENT STEP 1: Patients must have initiated their CDK 4/6 inhibitors within 30 days of the date of Step 0 registration OTHER: Electronic Health Record Review, OTHER: Health Promotion and Education, PROCEDURE: Health Telemonitoring, OTHER: Interview, BEHAVIORAL: Patient Navigation, OTHER: Survey Administration, OTHER: Text Message-Based Navigation Intervention
Anatomic Stage IV Breast Cancer AJCC v8, Breast Carcinoma, HER2-Negative Breast Carcinoma, Hormone Receptor-Positive Breast Carcinoma