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641 Study Matches
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) (MOVE FSHD)
Michaela Walker, MPH - mwalker20@kumc.edu
Johnson, Nicholas, E
NCT04635891
HM20021534
Inclusion Criteria:
* Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring.
Exclusion Criteria:
* Unwilling or unable to provide informed consent.
* Any other medical condition which in the opinion of the investigator would interfere with study participation. FSHD
Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation
Konrad S Famulski, PhD - konrad@ualberta.ca
NCT02670408
Inclusion Criteria:
* biopsy for clinical indications
Exclusion Criteria:
* no consent
* pregnant women PROCEDURE: Endomyocardial biopsy
Cardiac Transplant Disorder
Heart transplant, global gene expression, molecular diagnostics
Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM (EF-32)
Doron Manzur, MD - clinicaltrials@novocure.com
Harris, Timothy, James
NCT04471844
HM20024922
Inclusion Criteria:
• Histologically confirmed diagnosis of GBM according to WHO classification criteria.
• Age ≥ 22 years in US and Age ≥ 18 years in Ex-US
• Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
• Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2 daily x 5 d, q28 days)
• Karnofsky performance status ≥ 70
• Life expectancy ≥ least 3 months
• Participants of childbearing age must use highly effective contraception. An effective method of birth control is defined as one that results in a failure rate of less than 1% per year when used consistently and correctly. The Investigator must approve the selected method, and may consult with a gynecologist as needed.
• All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
• Stable or decreasing dose of corticosteroids for the last 7 days prior to randomization, if applicable.
• Concomitant RT with TMZ treatment planned to start no later than 8 weeks from surgery
• Women of childbearing potential must have a negative β-HCG pregnancy test documented within 14 days prior to registration
• Is able to have MRI with contrast of the brain
Exclusion Criteria:
• Progressive disease (per investigator's assessment)
• Infratentorial or leptomeningeal disease
• Participation in another clinical treatment study during the pre-treatment and/or the treatment phase of the study
• Pregnancy or breast-feeding.
• Significant co-morbidities at baseline which would preclude maintenance RT or TMZ treatment, as determined by the investigator:
• Thrombocytopenia (platelet count < 100 x 103/μL)
• Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
• CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
• Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
• Total bilirubin > 1.5 x upper limit of normal
• Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)
• History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
• Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
• History of hypersensitivity reaction to TMZ or a history of hypersensitivity to DTIC.
• Any other cytotoxic or biologic anti-tumor therapy received prior to enrollment will be considered exclusion.
• Admitted to an institution by administrative or court order.
• Known allergies to medical adhesives or hydrogel
• A skull defect (such as, missing bone with no replacement)
• Prior radiation treatment to the brain for the treatment of GBM
• Any serious surgical/post-operative condition that may risk the patient according to the investigator
• Standard TTFields exclusion criteria include
• Active implanted medical devices
• Bullet fragments
• Skull defects
Device: Optune®
Glioblastoma Multiforme
GBM
Total Neoadjuvant Therapy With mFOLFOX and Short-course Radiation in Resectable Rectal Cancer
Massey IIT Research Operations, RN - masseyepd@vcu.edu
Matin, Khalid
NCT04643366
HM20020384
Inclusion Criteria:
* Pathologic diagnosis of adenocarcinoma of the rectum (diagnosis by tissue biopsy) within 90 days prior to registration. At least a portion of the tumor must be located below the peritoneal reflection or begin within 12 cm of the anal verge on flexible endoscopy
* Clinically staged (AJCC 8th ed.) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup:
* Colonoscopy, unless patient presents with an obstructing lesion
* Within 30 days prior to registration:
* History/physical examination
* Imaging to exclude distant metastases: either contrast-enhanced CT of the chest, abdomen, and pelvis or whole-body PET-CT or MRI
* Pelvic MRI (preferred) or transrectal ultrasound (TRUS) for T staging Note: Patients may have initiated standard mFOLFOX6 treatment before study registration provided that they met the above criteria before initiating treatment and can feasibly continue to CRT according to the timeline described in Section
* ECOG Performance Status ≤2
* Age ≥ 18 years
* Adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3
* Platelets ≥ 100,000 cells/mm3
* Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥8.0 g/dL is acceptable.)
* Adequate liver and renal function defined as follows:
* AST and alkaline phosphatase \< 2.5 x upper limit of normal (ULN)
* Bilirubin ≤ 2.5 ULN
* Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft-Gault formula as calculated by the standard Cockcroft-Gault equation using age, actual weight, creatinine, and gender
* Must be deemed a candidate for curative resection by the surgical oncologist who will be performing the operation
* Women of childbearing potential (WCBP) must have a negative serum pregnancy test performed within 7 days prior to the start of chemotherapy.
* WCBP and men must agree to use a medically accepted form of birth control during the treatment and for 3 months following completion of chemotherapy.
* Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Prior RT that would result in unsafe overlap of RT fields with the planned study treatment, per the treating radiation oncologist
* Clinically significant cardiac disease, including major cardiac dysfunction, that in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin.
* Serious (ie, ≥ grade 3) uncontrolled infection
* Pulmonary or respiratory condition that, in the opinion of the treating medical oncologist would preclude them from receiving systemic therapy with 5-fluorouracil, leucovorin or oxaliplatin.
* Major surgery within 28 days of study enrollment (other than diverting colostomy)
* History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) requiring significant intervention (eg, hospitalization, surgery, immunosuppressive medications) that would, in the opinion of the investigator, preclude study therapy
* Prior known allergic reaction to 5-fluorouracil, leucovorin, or oxaliplatin
* Known dipyrimidine dehydrogenase deficiency (DPD)
* Any evidence of distant metastases (M1)
* Pregnant or breast feeding
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements DRUG: Chemotherapy, RADIATION: Radiation Therapy
Rectal Cancer
Resectable, Rectal
Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation (INTERLIVER)
Konrad S Famulski, PhD - konrad@ualberta.ca
NCT03193151
HM20012631
Inclusion Criteria:
* biopsy for clinical indications
Exclusion Criteria:
* no consent, pregnant women PROCEDURE: liver biopsy
Liver Dysfunction
Liver transplant, global gene expression, molecular diagnostics
Efficacy, Safety, And Pharmacokinetics Of Rifaximin In Subjects With Severe Hepatic Impairment And Hepatic Encephalopathy
Tendai Merriweather - tendai.merriweather@bauschhealth.com
NCT01846663
Inclusion Criteria:
• Male or non-pregnant, non-breast feeding female ≥ 18 years old
• In remission from demonstrated overt HE
• Had ≥1 episode of overt HE associated with liver disease within the last 6 months
• MELD score of ≥ 19
• Has a close family member or other personal contact who is familiar with the subject's HE, can provide continuing oversight to the subject and is willing to be available to the subject during the conduct of the trial
Exclusion Criteria:
• HIV
• History of tuberculosis infection
• Chronic respiratory insufficiency
• Current infection and receiving antibiotics
• Renal insufficiency requiring dialysis
• Active spontaneous bacterial peritonitis infection
• Intestinal obstruction or has inflammatory bowel disease
• Active malignancy within the last 5 years
• Current GI bleeding or has had a GI hemorrhage within past 3 months
• Anemia
Drug: Placebo, Drug: Rifaximin
Hepatic Encephalopathy
Hepatic Encephalopathy, Liver Failure, Hepatic Insufficiency, Liver Diseases, Brain Diseases, Rifaximin, Cirrhosis
NOURISH-T+: Promoting Healthy Eating and Exercise Behaviors (NOURISH-T+)
Marilyn Stern, PhD - mstern1@usf.edu
Mazzeo, Suzanne, E
NCT04656496
HM20019104
Inclusion Criteria:
Eligible Pediatric Cancer Survivors must be:
• 5-14 years of age at enrollment;
• Off active treatment for at least 6 months;
• At or above the 85th BMI %ile;
• Able to complete assessments with the help of clinic staff and the USF research team;
• Residing with the participating parent;
• Able to engage in PA tailored to current medical status;
• NOT taking medications that affect body weight (e.g., steroids) within 6 months of enrollment, and
• In remission -- PCS who experience a relapse of cancer during the intervention will be excused from further involvement.
• Must be English- or Spanish-speaking Participating Parents must: * Be either biological or adoptive and/or step mothers or fathers and must be permanent legal guardians of the PCS * Be at least 18 years old * Identifies as the main meal preparer at home * Must be English- or Spanish-speaking
Exclusion Criteria:
* Parents are ineligible if they are non-ambulatory and/or do not reside at least 50% of the time with their participating child.
* Female parents who are currently pregnant will be excluded from the study.
* Children are ineligible to participate if they are non-ambulatory. In addition, children who are wards of the state will be excluded from the study. BEHAVIORAL: NOURISH-T+, BEHAVIORAL: Brief NOURISH-T+
Obesity, Childhood, Cancer, Survivorship
Chemotherapy Induced Peripheral Neuropathy Natural History Study (EPIPHANY) (EPIPHANY)
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or - ClinicalTrials.gov@lilly.com
Smith, Albert Gordon
NCT03997981
HM20016182
Inclusion Criteria:
All of the following criteria must be met in order to be enrolled in the study:
• Age ≥18 years
• Life expectancy ≥6 months
• Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 CIPN (exception, patients with multiple myeloma treated with bortezomib, CTCAE Grade <=1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Breast cancer only:
• Breast cancer beginning treatment with paclitaxel or docetaxel with curative intent (i.e., not metastatic disease beyond regional lymph nodes)
• Planned minimum of 6 cycles of chemotherapy
• Lymphoma only:
• Incident lymphoma initiating treatment with vincristine
• Planned minimum of 4 cycles of chemotherapy
• Oxaliplatin-based regimens, Stage III colorectal cancer: Total of 6 months (planned minimum of 12 cycles). May consider Stage IV with minimal metastatic confirmed with Sponsor prior to enrollment
• Bortezomib use in untreated multiple myeloma: Total of 4 months (planned minimum of 9 cycles)
• Written informed consent given
• Enrollment must be completed prior to receiving the first dose of chemotherapy
Exclusion Criteria:
Patients meeting ANY of the following criteria are not eligible for participation:
• Evidence of central nervous system metastases
• Evidence of clinically significant peripheral neuropathy (CTCAE >2) as defined by patient report of frequent numbness or tingling in the hands or feet
• Any uncontrolled serious illness or medical condition that would impact the conduct of the current study
• Previous exposure to neurotoxic chemotherapy drugs
• Pre-existing neurodegenerative disease (Parkinson's, Alzheimer's, Huntington's, etc.), neuromuscular disorder (multiple sclerosis, ALS, polio, hereditary neuromuscular disease) or history of stoke or history of traumatic brain injury
• General anesthesia less than one month prior to the first dose of neurotoxic chemotherapy
drug: Vincristine,
drug: Paclitaxel,
drug: Oxaliplatin,
drug: Docetaxel,
drug: Bortezomib
Chemotherapy-induced Peripheral Neuropathy
CIPN
Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
Lantis, Kristin - kllantis@vcu.edu
Maher, Keri
NCT03739814
HM20021076
Inclusion Criteria:
* STEP 0: Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration. The specimens should be sent to the HEME Biobank.
* Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:
* Patients may receive the day 1 of course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then systemic chemotherapy must begin within 7 days of this IT chemotherapy.
* STEP 1: Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are not eligible.
* STEP 1: CD22-positive disease defined as CD22 expression by \>= 20% of lymphoblasts by local hematopathology evaluation.
* STEP 1: Philadelphia chromosome/BCR-ABL1-negative or Philadelphia chromosome/BCR-ABL1-positive B-cell ALL by cytogenetics, fluorescence in situ hybridization (FISH), and/or polymerase chain reaction (PCR).
* STEP 1: No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed). Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurological dysfunction) within the 28 days prior to registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for additional guidance. Prophylactic intrathecal medication alone is not an exclusion.
* Categories of CNS Involvement for CNS Evaluation Prior to Registration:
* CNS 1: CSF has \< 5 WBC/uL with cytospin negative for blasts; or \>= 10 red blood cell (RBC)/uL with cytospin negative for blasts.
* CNS 2: CSF has \< 5 WBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL, WBC/uL \>= 5 but less than Steinherz/Bleyer algorithm with cytospin positive for blasts (see below).
* CNS 3: CSF has \>= 5 WBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL, \>= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below); or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating Initial Traumatic Lumbar Punctures:
* If the patient has leukemia cells in the peripheral blood and the lumbar puncture is traumatic and contains \>= 5 WBC/uL with blasts, the following algorithm should be used to define CNS disease: CSF WBC/CSF RBC \> 2 x (Blood WBC/Blood RBC count)
* STEP 1: Patients with known or suspected testicular involvement by leukemia are allowed provided that the patient receives concomitant scrotal/testicular radiotherapy.
* Unilateral or bilateral testicular enlargement should be assessed by ultrasound or other imaging technique. Biopsy is recommended if clinical findings are equivocal or suggestive of hydrocele or a non-leukemic mass, but further assessments are per treating physician discretion.
* STEP 1: Not pregnant and not nursing.
* This study involves agents that have known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required.
* STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
* STEP 1: No unstable cardiac disease such as myocardial infarction, angina pectoris, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of registration.
* STEP 1: No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) \< 45% or New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF).
* STEP 1: Patients with known human immunodeficiency virus (HIV) infection are eligible if they have been on effective antiretroviral therapy with an undetectable viral load tested within 6 months of registration.
* STEP 1: Patients with hepatitis B virus (HBV) are eligible only if they meet all the following:
* On HBV-suppressive therapy.
* No evidence of active virus.
* No evidence of HBV-related liver damage.
* STEP 1: Patients with hepatitis C virus (HCV) are eligible only if they meet all the following:
* Successfully completed complete-eradication therapy with undetectable viral load.
* No evidence of HCV-related liver damage.
* STEP 1: No history of clinically relevant neurologic disorder such as epilepsy, seizure, aphasia, stroke, severe brain injury, structural brain abnormality, benign brain tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other significant CNS abnormalities.
* STEP 1: No prior additional malignancy (i.e. in addition to ALL) except adequately treated basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for \>= 2 years.
* STEP 1: No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal syncope, or chronic bradycardic states such as sinoatrial block or higher degree of atrioventricular block unless a permanent pacemaker has been implanted.
* STEP 1: No history of chronic liver disease, including cirrhosis.
* STEP 1: No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
* STEP 1: No uncontrolled infection or recent history (within 4 months prior to registration) of deep tissue infections such as fasciitis or osteomyelitis.
* STEP 1: Total bilirubin, serum =\< 1.5 x upper limit of normal (ULN)\*
* Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =\< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =\< 2 x ULN.
* STEP 1: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* STEP 1: Creatinine, serum =\< 1.5 ULN OR creatinine clearance \>= 40 mL/min
* STEP 1: QT interval by Fridericia's correction formula (QTcF) =\< 470 msec
* COHORT 1: Age \>= 60 years.
* COHORT 1: Diagnosis of Philadelphia chromosome/BCR-ABL1-negative B-cell ALL.
* COHORT 1: No prior treatment for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed therapy may be administered for no more than 14 days and must be completed \>= 24 hours prior to the initiation of protocol therapy.
* COHORT 1: No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
* COHORT 2: Age \>= 18 years.
* COHORT 2: Diagnosis of Philadelphia chromosome/BCR-ABL1-negative B-cell ALL.
* COHORT 2: Relapsed or refractory disease in salvage 1 or 2.
* COHORT 2: No isolated extramedullary relapse.
* COHORT 2: Prior allogeneic HCT permitted.
* COHORT 2: Patients with prior allogeneic HCT must have completed transplantation \>= 4 months prior to registration.
* COHORT 2: Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease and must have completed immunosuppressive therapy \>= 30 days prior to registration.
* COHORT 2: Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy, or other CD19-directed therapy is not allowed.
* COHORT 2: Prior treatment with rituximab must be completed \>= 7 days prior to registration.
* COHORT 2: Prior treatment with other monoclonal antibodies must be completed \>= 6 weeks prior to registration.
* COHORT 2: Prior treatment for ALL must be completed \>= 14 days prior to registration with the following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids, 6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce circulating absolute lymphoblast count to =\< 10,000/uL or prevent complications related to ALL are allowed but must be completed \>= 24 hours prior to the initiation of protocol therapy.
* COHORT 2: Patients should have resolution of any acute non-hematologic toxicities of prior therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 grade =\< 1.
* COHORT 2: Peripheral blood absolute lymphoblast count =\< 10,000/uL (treatment allowed as above to reduce blast count to =\< 10,000/uL)
* COHORT 3: Age ≥ 75 years OR age ≥ 18 years AND ineligible for hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HyperCVAD) regimens
* COHORT 3: Diagnosis of Philadelphia chromosome/BCR-ABL1-positive B-cell ALL
* COHORT 3: No prior treatment for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, BCR-ABL1-targeted tyrosine kinase inhibitor, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed non-protocol therapy may be administered for no more than 14 days and must be completed ≥ 24 hours prior to the initiation of protocol therapy.
* COHORT 3: No chronic, strong CYP3A4 inducers PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, BIOLOGICAL: Inotuzumab Ozogamicin, PROCEDURE: Lumbar Puncture, DRUG: Ponatinib
B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia
Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD)
Katherine Wu, MD - kwu@jhmi.edu
NCT00733590
Inclusion Criteria:
* History of acute MI at least 4 weeks old
* Non-ischemic LV dysfunction for at least 9 months
* Who have an ejection fraction (EF) \< or = to 35%
* Undergone elective replacement indicator (ERI) generator replacement of an FDA-approved ICD for primary prevention of SCD within 24 months of enrollment.
* Who have primary prevention implants.
Exclusion Criteria:
* ICD generator replacement for secondary prevention
* Inability or unwillingness to provide valid informed consent
* New York Heart Association Class IV heart failure
* Patients with pre-existing Class 1 indications for pacemaker therapy. Heart Failure, Congestive, Death, Sudden, Cardiac, Arrhythmia, Cardiomyopathies
defibrillator, implanted, genomics, electrocardiography, electrophysiological study, proteomics
A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants
OHB Contact - CMO@Oakhillbio.com
Rozycki, Henry
NCT03253263
HM20016299
Inclusion Criteria:
• Written informed consents and/or assents must be signed and dated by the participant's parent(s) prior to any study related procedures. The informed consent and any assents for underage parents must be approved by the IRB/IEC (in accordance with local regulations).
• Written informed consents and/or assents must be signed and dated by the participant's birth mother prior to providing study-related information related to birth mother medical history, pregnancy and the birth of the participant. The informed consent and any assents for underage birth mothers must be approved by the IRB/IEC (in accordance with local regulations).
• Subjects must be between 23 weeks +0 days and 27 weeks +6 days GA, inclusive.
Exclusion Criteria:
• Detectable major (or severe) congenital malformation identified before randomization.
• Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator's opinion.
• Hypoglycemia at Baseline (blood glucose less than (\<) 45 milligrams per deciliter \[mg/dL\] or 2.5 milli moles per liter \[mmol/L\]) which persists in spite of glucose supplementation, to exclude severe congenital abnormalities of glucose metabolism.
• Clinically significant neurological disease identified before randomization according to cranial ultrasound (hemorrhages confined to the germinal matrix are allowed) and investigator's opinion.
• Any other condition or therapy that, in the investigator's opinion, may pose a risk to the participant or interfere with the participant's potential compliance with this protocol or interfere with interpretation of results.
• Current or planned participation in a clinical study of another investigational study treatment, device, or procedure (participation in non-interventional studies is permitted on a case-by-case basis).
• The participant or participant's parent(s) is/are unable to comply with the protocol or is unlikely to be available for long-term follow-up as determined by the investigator.
• Birth mother with active COVID-19 infection at birth or a history of severe COVID-19 infection (requiring intensive care hospitalization) during pregnancy.
• Birth mother with known HIV or hepatitis (B, C, or E) infection.
DRUG: OHB-607
Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity, Intraventricular Hemorrhage, Retinopathy of Prematurity (ROP)
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk)
Washington, Sonya, L - slwashington@vcu.edu
Sullivan, Stephanie, A
NCT04251052
HM20020403
Inclusion Criteria:
* Individuals 35-50 years of age, inclusive
* Patients who will undergo risk-reducing salpingo-oophorectomy (RRSO) (for the BSO arm) and patients who have declined or elected to defer BSO after proper counselling to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned hysterectomy with either arm is permitted
* At least one intact ovary and fallopian tube is in situ at the time of counseling, consent, and registration. Prior hysterectomy is allowed provided it did not include bilateral salpingectomy. Prior tubal ligation is allowed if one ovary and fallopian tube (with fimbria not removed) are present
* Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation of the result is required
* Patients may be premenopausal or menopausal
* Pelvic ultrasound (transvaginal imaging preferred, but transabdominal imaging is acceptable) or pelvic MRI and CA-125 within 180 days of registration
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* Individuals who are currently pregnant or plan to become pregnant in the future through assisted reproductive technologies and who have received proper counseling are eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at the time of a planned cesarean section are eligible. Patients must understand that they will not be able to become pregnant naturally in the future
Exclusion Criteria:
* Individuals with a history of any prior cancer who have received cytotoxic chemotherapy within the past 30 days or radiotherapy to abdomen or pelvis at any prior time. Endocrine therapy or maintenance ERBB2/HER2 targeted therapy is allowed. Maintenance immune checkpoint inhibitor therapy is allowed. Maintenance therapy with PARP in inhibitor is allowed.
* Prior history of ovarian cancer, including low malignant potential neoplasms (LMP), primary peritoneal carcinoma, or fallopian tube carcinoma
* Patients medically unfit for the planned surgical procedure
* Patients with abnormal screening tests (pelvic ultrasound, pelvic MRI, CA-125) suspicious for occult or gross pelvic malignancy within the past 180 days
* An abnormal pelvic ultrasound (or pelvic MRI) is defined as morphologic or structural variations suspicious for ovarian malignancy. Complex cystic lesions felt to represent a benign lesion are not exclusionary. Simple cysts of any size are not exclusionary
* An abnormal CA-125 is defined as a level \> 50U/ml in premenopausal individuals if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level \> 40U/ml for premenopausal individuals who are current users of oral contraceptives (Skates 2011). An abnormal CA-125 is defined as a level \> 35 U/ml in postmenopausal individuals PROCEDURE: Bilateral Salpingectomy, PROCEDURE: Bilateral Salpingectomy with Oophorectomy, PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, PROCEDURE: Transvaginal Ultrasound, PROCEDURE: Ultrasound Imaging
Ovarian Carcinoma
National Cancer Institute "Cancer Moonshot Biobank" (moonshot)
Castellanos, Natasha, Guzy - castellanosn@vcu.edu
Poklepovic, Andrew, S
NCT04314401
HM20020956
Inclusion Criteria:
* Is consistent with OR has been diagnosed with one of the following:
* Colorectal cancer: stage IV
* Non-small cell or small cell lung cancer: stage III/IV
* Prostate cancer: metastatic prostate cancer
* Gastric cancer, not otherwise specified (NOS): stage IV
* Esophageal cancer, NOS: stage IV
* Adenocarcinoma of gastroesophageal junction: stage IV
* High grade serous ovarian cancer: stage III/IV
* Invasive breast carcinoma: stage III/IV
* Melanoma: stage III/IV
* Acute myeloid leukemia
* Multiple myeloma
* For the purposes of this study,
* Re-staging is allowed
* Having more than one primary cancer is allowed, if the patient is being treated solely for one of the eligible cancers listed above
* Patient should fit in one of the following four clinical scenarios (a-d)
* Undergoing diagnostic workup for one of the diseases listed for which treatment will likely include a new regimen of standard of care therapy OR
* Scheduled to begin treatment with a new regimen of standard of care therapy OR
* Currently progressing on a regimen of standard of care therapy OR
* Currently being treated with a regimen standard of care therapy, without evidence of progression
* Requirements for fresh tissue biospecimen collections at enrollment:
* For clinical scenarios a, b, and c above, freshly collected tumor tissue or bone marrow (BM) aspirate must be submitted at enrollment
* For clinical scenarios a and b, the fresh tissue collection must be prior to starting therapy
* For clinical scenario a, the biospecimen collection must be part of a standard of care medical procedure
* For clinical scenarios b or c, the biospecimen collection may be part of a standard of care medical procedure OR
* The biospecimen collection may be part of a study-specific procedure ("research only biopsy"), when the patient has a tumor amenable to image guided or direct vision biopsy and is willing and able to undergo a tumor biopsy for molecular profiling
* Note: For research-only biopsies, the biopsy must not be associated with a significant risk of severe or major complications or death; the procedure cannot be a mediastinal, laparoscopic, open or endoscopic biopsy; nor can the procedure be a brain biopsy; nor can the patient be under the age of majority as determined by each U.S. state
* Requirements for archival tissue:
* For clinical scenarios a and b above, archival tissue as outlined below must be submitted IF AVAILABLE
* For clinical scenarios c and d above, archival tissue as outlined below is REQUIRED
* Pre-existing archival material (formalin-fixed, paraffin-embedded \[FFPE\] block, BM aspirate, or unstained slides) that:
* Contains the cancer type for which the participant is enrolled, and
* Was collected no more than 5 years prior to initiation of therapy, and
* Contains at least a surface area of 5 mm\^2 and optimal surface area of 25 mm\^2 or 3-5 mL cryopreserved bone marrow aspirate to yield 200 million bone marrow mononuclear cells, and
* Contains at least 10% tumor content. 70% tumor content is optimal, and
* No more than 1 line of standard of care systemic therapy was administered from the date of archival material collection to the date of initiation of therapy
* Requirements for blood collection: ALL scenarios require fresh blood collection at enrollment
* Blood collection for clinical scenarios a, b, and c must take place within 1 week of fresh tumor specimen collection
* Blood collection for clinical scenario d must take place within 4 weeks of enrollment, and while patient is on treatment
* Age 13 or older
* Any sex
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
* Ability to understand and willingness to sign an informed consent document. Consent may be provided by a Legally Authorized Representative (LAR) in accordance with 45 CFR 46.102(i)
* NCI PDMR INCLUSION CRITERIA: Patients with CRC with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status
* NCI PDMR INCLUSION CRITERIA: Patients with CRC who are 40 years old or younger at time of collection irrespective of mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) status
* NCI PDMR INCLUSION CRITERIA: Patients with BRCA that are either
* Any race/ethnicity with hormone receptor positive (ER+PR+, ER+PR-, or ER-PR+)
* African American with triple negative (ER-PR-HER2-)
* NCI PDMR INCLUSION CRITERIA: Patients with lung cancer (LCA), prostate cancer (PCA), gastroesophageal cancer (GEC), ovarian cancer (OV), acute myeloid leukemia (AML), multiple myeloma (MML)
Exclusion Criteria:
* Treated with or has already begun treatment with a non-standard of care therapeutic agent (investigational) in an interventional clinical trial
* For the purposes of this study, past enrollment in clinical trials whereby the patient was randomized and treated with standard-of-care anti-cancer treatment (chemotherapy regimen, surgery and radiation therapy) is allowed
* Uncontrolled intercurrent illness that in the physician's assessment would pose undue risk for biopsy
* Use of full dose coumarin-derivative anticoagulants such as warfarin are prohibited. Patients may be switched to low molecular weight (LMW) heparin at physician discretion
* Low molecular weight (LMW) heparin is permitted for prophylactic or therapeutic use
* Factor X inhibitors are permitted
* Use of anti-platelet drugs are permitted
* Stopping the anticoagulation treatment for biopsy, bone marrow aspirate, or resection should be per site standard operating procedure (SOP)
* NCI PDMR EXCLUSION CRITERIA: Patients with complete response
* NCI PDMR EXCLUSION CRITERIA: Patients with invasive fungal infections
* NCI PDMR EXCLUSION CRITERIA: Patients with active and/or uncontrolled infections or who are still recovering from an infection
* Actively febrile patients with uncertain etiology of febrile episode
* All antibiotics for non-prophylactic treatment of infection should be completed at least 1 week (7 days) prior to collection
* No recurrence of fever or other symptoms related to infection for at least 1 week (7 days) following completion of antibiotics
* NCI PDMR EXCLUSION CRITERIA: Patients with human immunodeficiency virus (HIV), active or chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-deoxyribonucleic acid \[DNA\] and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]) or known history of HBV/HCV without documented resolution PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, OTHER: Medical Chart Review, PROCEDURE: Paracentesis, PROCEDURE: Positron Emission Tomography
Acute Myeloid Leukemia, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Esophageal Carcinoma, Fallopian Tube Carcinoma, Gastric Carcinoma, Hormone Receptor-Positive Breast Carcinoma, Invasive Breast Carcinoma, Lung Non-Small Cell Carcinoma, Lung Small Cell Carcinoma, Malignant Solid Neoplasm, Melanoma, Metastatic Prostate Carcinoma, Multiple Myeloma, Ovarian Carcinoma, Ovarian High Grade Serous Adenocarcinoma, Primary Peritoneal Carcinoma, Stage III Fallopian Tube Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Triple-negative Breast Carcinoma
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b
Jamie Barrett - medicalinformation@mersana.com
Randall, Leslie
NCT03319628
HM20020050
General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):
• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9 g/dL
• In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
• Estimated glomerular filtration rate (GFR) ≥45 mL/min
• Total bilirubin ≤ULN
• g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent. General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :
• Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
• Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Current use of either constant or intermittent supplementary oxygen therapy.
• History of suspected pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
• Oxygen saturation on room air <93% Ovarian Cancer Inclusion Criteria for UPLIFT:
• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.
• Platinum-resistant disease
• Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
• Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum
• One to 4 prior lines of systemic therapy for ovarian cancer a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure Ovarian Cancer Exclusion Criteria for UPLIFT:
• Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
• Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
• Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
• Participation in DES or EXP segments of this study Ovarian Cancer Inclusion Criteria for QTc sub-study: Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study • Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3. Ovarian Cancer Exclusion Criteria for QTc sub-study:
• Use of strong CYP450 3A inducers.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening with HR >45- <100
• Any ECG abnormality that can interfere with the measurement of the QT interval
• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9 g/dL
• In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
• Estimated glomerular filtration rate (GFR) ≥45 mL/min
• Total bilirubin ≤ULN
• g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent. General Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :
• Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
• Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
• Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
• Current use of either constant or intermittent supplementary oxygen therapy.
• History of suspected pneumonitis or interstitial lung disease.
• Pregnant or nursing women.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
• Oxygen saturation on room air <93% Ovarian Cancer Inclusion Criteria for UPLIFT:
• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.
• Platinum-resistant disease
• Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
• Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum
• One to 4 prior lines of systemic therapy for ovarian cancer a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure Ovarian Cancer Exclusion Criteria for UPLIFT:
• Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
• Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
• Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
• Participation in DES or EXP segments of this study Ovarian Cancer Inclusion Criteria for QTc sub-study: Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study • Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3. Ovarian Cancer Exclusion Criteria for QTc sub-study:
• Use of strong CYP450 3A inducers.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening with HR >45- <100
• Any ECG abnormality that can interfere with the measurement of the QT interval
Drug: upifitamab rilsodotin
Platinum Resistant Ovarian Cancer, Non Small Cell Lung Cancer Metastatic
Cardiac Resynchronization Therapy in Previously Untreatable and High Risk Upgrade Patients (SOLVE-CRT)
Nicholas Vesom - clinical@ebrsystemsinc.com
Ellenbogen, Kenneth, A
NCT02922036
HM20014794
Inclusion/Exclusion:
Inclusion Criteria
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
• Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
• Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
• Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms
• Patient is a:
• 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
• EF has remained unchanged or worsened (defined as < 5% increase since implant), and
• The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee OR
• 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons: i. Patients in whom CS lead implantation for CRT has failed
• CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges ii. CS lead implanted but has been programmed OFF
• LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location OR c. 'High Risk Upgrade: Patients who have a relative contraindication to CS lead implant, due to:
• venous occlusion or lesion precluding implant
• pocket infection risk (at co-implanted device site)
• considered high risk for CS implant due to co-morbidities
• Patients on a stable Guideline Directed Medical Therapy (GDMT)
• Patient must be 18 years old or over
• Patient has signed and dated informed consent
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant) Exclusion Criteria Patients who meet any one of these criteria will be excluded from the investigation:
• Pure RBBB
• LVEDD ≥ 8cm
• Non-ambulatory or unstable NYHA class IV
• Contraindication to heparin, chronic anticoagulants or antiplatelet agents
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant
• Life expectancy of < 12 months
• Chronic hemodialysis
• Stage 4 or 5 renal dysfunction defined as eGFR < 30
• Grade 4 mitral valve regurgitation
• Noncardiac implanted electrical stimulation therapy devices
• Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
• Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month
• Correctable valvular disease that is the primary cause of heart failure
• Recent CVA or TIA (within the previous 3 months)
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
• Already included in another clinical study that could confound the results of this study
• Pregnancy
• Known drug or alcohol addiction or abuse
• Moderate or severe aortic stenosis
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
• For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months
Device: WiSE System
Heart Failure
STRIDE Biorepository
Lakshmanan Krishnamurti, MD - lakshmanan.krishnamurti@emory.edu
NCT02843347
Inclusion Criteria:
• Age at least 15 years old to less than 41 years old
• Severe sickle cell disease [any clinically significant sickle genotype, for example, Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb S?), or Hemoglobin S-OArab genotype] with at least 1 of the following manifestations:
• Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy);
• An average of three or more pain crises per year in the 2-year period preceding enrollment or referral (required intravenous pain management in the outpatient or inpatient hospital setting);
• Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year(in the 12 months before enrollment to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome);
• An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ?
• 7 m/sec;
• Ongoing high impact chronic pain on a majority of days per month for at least 6 months.
• Adequate physical function as measured by all of the following:
• Karnofsky/Lansky performance score > or equal to 60
• Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition (MUGA) Scan
• Pulmonary function: Pulse oximetry with a baseline O2 saturation of ? 85% and diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin)
• Renal function: Serum creatinine ? 1.5 x the upper limit of normal for age as per local laboratory and creatinine clearance >70 mL/min; or GFR > 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR)
• Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal as per local laboratory.
Exclusion Criteria:
• Human Leukocyte Antigen (HLA) typing prior to referral (consultation with hematopoietic cell transplantation (HCT) physician). However, if a subject has had HLA typing with accompanying documentation that relatives were not HLA typed and that a search of the unrelated donor registry was not performed the subject will be considered eligible. Documentation will be reviewed and adjudicated by the Protocol Officer or his/her designee.
• Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
• Seropositivity for HIV
• Previous HCT or solid organ transplant
• Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
• A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
• Demonstrated lack of compliance with prior medical care (determined by referring physician).
• Pregnant or breast feeding females.
• Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy. Additional Eligibility Criteria for Transplant after Biologic Assignment to the Donor Arm: Participants assigned to the Donor Arm at the time of biologic assignment are subject to additional transplant eligibility criteria as specified below. Additional, repeat clinical assessments prior to transplant should be obtained in accordance with institutional policies and standards of care in the interest of good clinical practice.
• Participants must have liver magnetic resonance imaging (MRI) (at least 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ?8 packed red blood cell transfusions for ?1 year or have received ?20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ?7 mg Fe/g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis, and active hepatitis (at least 90 days prior to initiation of transplant conditioning).
• Cerebral MRI/magnetic resonance angiogram (MRA) within 30 days prior to initiation of transplant conditioning. If there is clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) subjects will be deferred for at least 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation.
• Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications. This is to be documented in the medical record corresponding with the consent conference.
• Have a suitably matched HLA donor
• Willing and able to donate bone marrow
• Absence of anti-donor HLA antibodies
Procedure: Blood draw
Anemia, Sickle Cell
Biorepository, Genetics
PANTHER Study of Terumo Aortic Knitted and Woven Grafts, and Cardiovascular Patches (PANTHER)
Clinical Study Manager - r.smith1@terumoaortic.com
NCT04545502
Inclusion Criteria:
* Patients must meet all of the following inclusion criteria in order to be eligible for inclusion in the study:
All Patients:
* Patient meets the minimum age as per local regulations at time of consent
* Patient requires treatment with study device(s) according to the IFU(s)
* Patient is willing and able to comply with all SOC procedures and study visits
* Patient or their legally authorised representative (LAR) has given written informed consent to participate in study, including consent to collect data retrospectively
* For prospective emergency patients, retrospective consent is permissible
* For retrospective patients who are deceased at time of enrollment, local EC regulations relating to consent process should be followed.
Retrospective Patients only:
* Patient has a minimum of 1 year post-operative follow-up data available, or complete data to death.
* Patient implant date is no more than 5 years prior to study start date.
Exclusion Criteria:
* Any patient who meets any of the following exclusion criteria will be excluded from participation in the study:
* Patient is unable or unwilling to comply with the SOC procedures or follow-up regime
* Patient is contraindicated per the device IFU
* Patient has any other medical, social or psychological problems that in the opinion of the investigator preclude them from receiving this treatment and the procedures and evaluations pre- and post-procedure DEVICE: Gelsoft Plus Vascular Graft, DEVICE: Vascular Bypass Graft, DEVICE: Cardiovascular Patch, DEVICE: Gelweave Vascular Graft, DEVICE: Gelweave Valsalva Vascular Graft
Aneurysm, Dissection, Aortic Root Aneurysm, Aortic Root Dissection, Carotid Artery Injuries, Aortic Arch, Bypass Extremity Graft, Occlusive Vascular Disease, Aortic Diseases
Vascular Surgery
Testing the Addition of Radiation Therapy to the Usual Immune Therapy Treatment (Atezolizumab) for Extensive Stage Small Cell Lung Cancer, The RAPTOR Trial (RAPTOR)
Hamilton, Melanie, R - mrhamilton2@vcu.edu
Weiss, Elisabeth
NCT04402788
HM20020924
Inclusion Criteria:
* Any confirmation (cytologic, histologic, or pathologic) of extensive stage small cell lung cancer at any site, either primary or metastases
* Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography \[PET\]/computed tomography \[CT\] scan, diagnostic CT scan, magnetic resonance imaging \[MRI\] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum (if not receiving PCI) or 6 weeks from completion of prophylactic cranial irradiation (PCI)
* NOTE: Patients must have at least 3 cycles of E/P plus atezolizumab. They can have one cycle of induction E/P without concurrent atezolizumab if unable to receive concurrent E/P combined with atezolizumab for all cycles of induction therapy
* Patients must have measurable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment
* At time of enrollment after induction E/P chemotherapy and atezolizumab, if there is a pleural effusion, patients will be eligible if thoracentesis is cytologically negative or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
* Appropriate stage for study entry based on the following diagnostic workup:
* History/physical examination within 14 days prior to registration;
* Imaging within 42 days prior to registration to include:
* MRI brain with contrast or CT brain with contrast
* CT chest, abdomen and pelvis or whole body PET/CT scan any time after the fourth cycle of chemotherapy and prior to registration
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,000/cells/mm\^3 (within 14 days prior to registration)
* Platelets \>= 75,000 cells/mm\^3 (within 14 days prior to registration)
* Hemoglobin \>= 8 g/dL (within 14 days prior to registration)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN (AST and/or ALT =\< 5 ULN for patients with liver involvement) (within 14 days prior to registration)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration)
* Adequate renal function = Creatinine clearance \>=40 mL/min by the Cockcroft-Gault (C-G) equation: (within 14 days prior to registration)
* Upfront radiation therapy of symptomatic metastatic site is permissible if causing symptoms such as pain or impending fracture
* Patients with brain metastases are eligible after receiving whole brain radiation before enrollment (anytime during induction systemic therapy). Whole brain radiation can be delivered with hippocampal sparing or 3-D conformal technique. Patients with irradiated brain metastases are eligible if they are clinically stable from a neurological standpoint after completing radiotherapy (e.g. not having uncontrolled seizures) and do not require use of steroids above a dose of 10 mg of prednisone daily
* For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.
* Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
* Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
* Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months and a stable regimen of highly active anti-retroviral (HAART) HIV-positive patients must have no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Metastatic disease invading the liver (\> 3 metastases), heart or \> 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan counts as one site
* Patients with a concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen with atezolizumab or radiation
* Prior radiotherapy in the thorax that would result in overlapping RT fields, unless the overlapping fields meet acceptable dose constraints for normal tissue
* Active autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
* If the autoimmune disease is not active for over 3 years and the patient is not receiving immunosuppressive treatment such as methotrexate or steroids above a dose equivalent to 10 mg prednisone daily, the patient is eligible.
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
* Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations are excluded only if they have active disease with acute exacerbation and on immunosuppressive medications within the 12 months prior to enrollment. They are eligible otherwise.
* Severe, active co-morbidity defined as follows:
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
* Active tuberculosis;
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test)
* Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL);
* Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of \> 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary;
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months;
* History of recent myocardial infarction within 6 months prior to registration.
* Clinically significant interstitial lung disease
* Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Women who are breastfeeding and unwilling to discontinue
* History of allogeneic organ transplant
* Patients who have had immunotherapy-induced pneumonitis DRUG: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy
Extensive Stage Lung Small Cell Carcinoma
A Study of Auxora in Patients With Acute Pancreatitis and Accompanying SIRS (CARPO)
Liisa Tingue - liisa@calcimedica.com
Leichtle, Stefan, W
NCT04681066
HM20018952
Inclusion Criteria:
All of the following must be met for a patient to be randomized into the study:
• The diagnosis of acute pancreatitis has been established by the presence of abdominal pain consistent with acute pancreatitis together with at least 1 of the following 2 criteria:
• Serum lipase > 3 times the upper limit of normal (ULN);
• Characteristic findings of acute pancreatitis on abdominal imaging;
• The diagnosis of SIRS has been established by the presence of at least two of the following four criteria:
• Temperature < 36°C or > 38°C;
• Heart rate > 90 beats/minute;
• Respiratory rate >20 breaths/minute or arterial carbon dioxide tension (PaCO2) <32 mmHg;
• White blood cell count (WBC) >12,000 mm3, or <4,000 mm3, or > 10% immature (band) forms;
• At least one of the following criteria is also present:
• A peripancreatic fluid collection or a pleural effusion on a contrast-enhanced computed tomography (CECT) performed in the 24 hours before Consent or after Consent and before Randomization;
• Abdominal examination documenting either abdominal guarding or rebound tenderness;
• Hematocrit ≥44% for men or ≥40% for women;
• The patient is ≥ 18 years of age;
• Lack of pancreatic necrosis, pancreatic calcifications, pancreatic pseudocysts and no evidence for previous necrosectomy or pancreatic surgery identified by CECT performed in the 24 hours before Consent or after Consent and before Randomization;
• A female patient of childbearing potential who is sexually active with a male partner is willing to practice acceptable methods of birth control for 180 days after the last dose of study drug. A female patient must not attempt to become pregnant for 180 days;
• A male patient who is sexually active with a female partner of childbearing potential is willing to practice acceptable methods of birth control for 180 days after the last dose of study drug. A male patient must not donate sperm for 180 days;
• The patient is willing and able to, or has a legal authorized representative (LAR) who is willing and able to, provide informed consent to participate, and to cooperate with all aspects of the protocol.
Exclusion Criteria:
Patients with any of the following conditions or characteristics must be excluded from
randomizing:
• Expected survival <6 months;
• Suspected presence of cholangitis in the judgment of the treating physician;
• The patient has a known history of:
• Organ or hematologic transplant;
• HIV, hepatitis B, or hepatitis C infection;
• Chronic pancreatitis;
• Current treatment with:
• Chemotherapy;
• Immunosuppressive medications or immunotherapy
• Pancreatic enzyme replacement therapy;
• Hemodialysis or Peritoneal Dialysis;
• The patient is known to be pregnant or is nursing;
• The patient has participated in another study of an investigational drug or therapeutic medical device in the 30 days before randomization;
• Allergy to eggs or known hypersensitivity to any components of study drug.
Drug: CM-4620 Injectable Emulsion or CM-4620-IE, Other: Placebo
Acute Pancreatitis, Systemic Inflammatory Response Syndrome
Evaluating the Safety and Efficacy of Polyethylene Glycol (PEG) Mediated Fusion (PEG Fusion)
Elizabeth Wysocki, MS - ewysock2@jhu.edu
NCT04789044
Inclusion Criteria:
• Ages 18-80
• Sustained a complete peripheral nerve injury resulting from upper extremity trauma presenting within 48 hours of injury
• Involves injury or dysfunction to motor and/or sensory function of the axillary, radial, median, ulnar, or musculocutaneous nerve with injury localized between the proximal humerus and the distal flexion crease of the wrist
• Involves a "mixed" nerve segment (i.e., involves a location of any of the above specified nerves that can be expected to have both sensory and motor axons present).
Exclusion Criteria:
• Patients beginning surgery within hours after injury.
• Injury to the brachial plexus nerves
• Injury to the nerves distal to the distal flexion crease of the wrist
• Injury that involves a distal extension of the parent nerve that is considered sensory only (superficial radial nerve, lateral antebrachial cutaneous nerve, etc.) or the posterior interosseus or anterior interosseus nerve distal to the midpoint of the forearm (i.e., distal to what can be considered the main motor branches of the PIN and AIN).
• Previous peripheral nerve injury resulting from trauma, stroke, muscular, neurologic, or neuromuscular disorder
• Documented psychiatric disorder that is expected to result in high probability of self-harm or interfere with study follow-up.
• Severe problems with maintaining follow up (e.g., patients who are prisoners or homeless at time of injury or who are intellectually challenged without adequate family support).
• Not expected to survive the next 30 days due to their injuries/health condition.
• The subject has a known allergy to polyethylene glycol (PEG).
• If any of the assessments cannot be done on the contralateral side (CL) or the MRCC sensory 2PD value is \> 10 mm on the CL side during baseline period, the subject is a screen failure.
• The subject is pregnant and/or is breastfeeding.
• The subject has a significant medical comorbidity precluding immediate repair.
• The subject is not able to strictly adhere to the rules of the current clinical protocol.
DRUG: NTX-001
Peripheral Nerve Injuries
A Study to Evaluate the Safety and Efficacy of Satralizumab in Participants With Neuromyelitis Optica Spectrum Disorder (NMOSD)
Reference Study ID Number: WN42349 www.roche.com/about_roche/roche_worldwide.htm - global-roche-genentech-trials@gene.com
NCT04660539
Inclusion Criteria:
• Participants aged less than 18 years at the time of informed consent for Study BN40898 can continue treatment with a combination of oral corticosteroids and either AZA or MMF
• Participated in Study BN40898 or Study BN40900 with satralizumab in NMOSD, are on ongoing satralizumab treatment and were anti-aquaporin-4 IgG antibody (AQP4-IgG) seropositive at screening in these studies. Participants with NMOSD who were AQP4-IgG seronegative at screening in Study BN40898 or Study BN40900 can be enrolled if the investigator considers the continued treatment with satralizumab to be beneficial for the participant
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 3 months after the final dose of satralizumab.
Exclusion Criteria:
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of study drug. Women of childbearing potential must have a negative urine pregnancy test result on the baseline visit prior to initiation of study drug
• Evidence of any serious uncontrolled concomitant diseases that may preclude participation including nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency
• Known active infection that requires delaying the next satralizumab dose at the time of enrollment
• NMOSD relapse at the time of enrollment
• Laboratory abnormalities at the last assessment in Study BN40898 or Study BN40900 that preclude re-treatment with satralizumab
Drug: satralizumab, Drug: azathioprine (AZA), Drug: mycophenolate mofetil (MMF), Drug: oral corticosteroids
Neuromyelitis Optica Spectrum Disorder
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Griffin, Jordyn
NCT04293562
HM20020887
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
* Patient must have 1 of the following:
* \>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
* In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* \< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
* A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count \>= 10,000/uL with \>= 10% blasts or a WBC count of \>= 5,000/uL with \>= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
* ARM C: Patient must be \>= 2 years of age at the time of Late Callback
* ARM C: Patient must have FLT3/ITD allelic ratio \> 0.1 as reported by Molecular Oncology
* ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
* ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* ARM D: Patient must be \>= 2 years of age at the time of Late Callback
* ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
* ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
* NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
* NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
* NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
* NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Fanconi anemia
* Shwachman Diamond syndrome
* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
* Telomere disorders
* Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
* Any concurrent malignancy
* Juvenile myelomonocytic leukemia (JMML)
* Philadelphia chromosome positive AML
* Mixed phenotype acute leukemia
* Acute promyelocytic leukemia
* Acute myeloid leukemia arising from myelodysplasia
* Therapy-related myeloid neoplasms
* Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) \< 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) \< 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF \>= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
* Administration of prior anti-cancer therapy except as outlined below:
* Hydroxyurea
* All-trans retinoic acid (ATRA)
* Corticosteroids (any route)
* Intrathecal therapy given at diagnosis
* In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* ARM D: Patient does not have any congenital long QT syndrome or congenital heart block PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexrazoxane Hydrochloride, DRUG: Etoposide, OTHER: Fludeoxyglucose F-18, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib Fumarate, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, DRUG: Mitoxantrone Hydrochloride, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, DRUG: Therapeutic Hydrocortisone
Acute Myeloid Leukemia
Preventing Retaliatory Gun Violence in Violently Injured Adults
Nicholas Thomson - Nicholas.Thomson@vcuhealth.org
NCT04813185
Inclusion Criteria:
* They receive treatment in the hospital for a violence-related injury (e.g., gunshot wound)
* They are 18 years or older
* They are English speaking
* They are eligible for BTG services (which includes living within the BTG catchment area for the hospital; Richmond City and neighboring counties)
Exclusion Criteria:
* Non-English speaking
* Age \<18
* Prisoners BEHAVIORAL: Bridging the Gap
Violence
Colorectal Health Research Champions
Hunley, Rachel - rachel.hunley@vcuhealth.org
Sheppard, Vanessa, B.
NCT04812743
HM20017398
Inclusion Criteria:
the individual is > 30 years of age
• They are literate
• They are/were directly or indirectly impacted by colorectal cancer and interested in becoming a champion for colorectal cancer research. To participate in a chat hosted by the CHRC the inclusion criteria is:
• adult of any gender
• over 30 years of age. Exclusion Criteria for chat hosted by the CHRC: -Those < 30 years of age
Behavioral: Colorectal Health Research Champions
Cancer of Colon, Cancer of Rectum, Rectum, Colon
Prevention
Crystalloids Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS)
Mason, Jessica - jessica.mason1@vcuhealth.org
de Wit, Marjolein
NCT03434028
HM20013528
Inclusion Criteria:
• Age ? 18 years
• A suspected or confirmed infection (broadly defined by administration or planned administration of antibiotics)
• Sepsis-induced hypotension defined as systolic blood pressure < 100 mmHg or MAP < 65 mmHg after a minimum of at least 1 liter of fluid (*Fluids inclusive of pre-hospital fluids; blood pressure must be below any known or reported pre-morbid baseline).
Exclusion Criteria:
• More than 4 hours elapsed since meeting inclusion criteria or 24 hours elapsed since admission to the hospital
• Patient already received 3 liters of intravenous fluid (includes prehospital volumes)
• Unable to obtain informed consent
• Known pregnancy
• Hypotension suspected to be due to non-sepsis cause (e.g. hemorrhagic shock)
• Blood pressure is at known or reported baseline level
• Severe Volume Depletion from an acute condition other than sepsis. In the judgment of the treating physician, the patient has an acute condition other than sepsis causing (or indicative) of *severe volume depletion; Examples include: Diabetic ketoacidosis, high volume vomiting or diarrhea, hyperosmolar hyperglycemic state, and nonexertional hyperthermia (heat stroke); severe is defined by the need for substantial intravenous fluid administration as part of routine clinical care
• Pulmonary edema or clinical signs of new fluid overload (e.g. bilateral crackles, new oxygen requirement, new peripheral edema, fluid overload on chest x-ray)
• Treating physician unwilling to give additional fluids as directed by the liberal protocol
• Treating physician unwilling to use vasopressors as directed by the restrictive protocol.
• Current or imminent decision to withhold most/all life-sustaining treatment; this does not exclude those patients committed to full support except cardiopulmonary resuscitation
• Immediate surgical intervention planned such that study procedures could not be followed
• Prior enrollment in this study
Drug: Early Vasopressors, Drug: Early Fluids,
drug: Ringer's (hartmann's) lactate solution,
drug: Plasmalyte (crystalloid) solution,
drug: Normal (0.9%, isotonic) saline solution,
drug: Norepinephrine
Septic Shock, Symptoms, Signs, and lll-Defined Conditions (780-799)
Fluid management, Sepsis-induced hypotension, vasopressors
IBP-9414 for the Prevention of Necrotizing Enterocolitis - The Connection Study
Subotic, Aleksander - aleksandar.subotic@vcuhealth.org
Moores, Russell, Ray
NCT03978000
HM20018843
Inclusion Criteria:
• Gestational age at birth of 23 weeks+0 days to 32 weeks+0 days
• Birth weight 500-1500g
• ? 48 hours of age
• Written informed consent from the subject?s legally authorized representative (LAR)
Exclusion Criteria:
• Participation in any other interventional clinical trial
• Infants in extremis to whom no further intensive care is offered by attending neonatologist
• Infants with, or at a high probability for, early onset sepsis
• Infants with recognized chromosomal anomalies
• Congenital or acquired gastrointestinal disease
• Earlier or planned administration of formulas, foods or supplements that contain added live bacteria
• Infants with known positive maternal HIV status
Drug: IBP-9414, Drug: Placebo,
drug: Ibp-9414
Necrotizing Enterocolitis, Certain Conditions Originating in the Perinatal Period (760-779)
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
Lantis, Kristin - kllantis@vcu.edu
Maher, Keri
NCT04530565
HM20021870
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* 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 registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior 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
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* 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 must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT) and ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1
Givinostat in Duchenne's Muscular Dystrophy Long-term Safety and Tolerability Study
Reference Study ID Number: DSC/14/2357/51 - patientadvocacy@italfarmaco.com
Harper, Amy
NCT03373968
HM20018448
Inclusion Criteria:
• Must have participated in one of the previous studies with GIVINOSTAT in DMD and have attended the End of Study Visit or must have been screened in study DSC/14/2357/48 and met: * all the inclusion criteria and none of the exclusion criteria, * had a baseline vastus lateralis muscle fat fraction (VL MFF) assessed by MRS in the range ≤5% or \>30%, i.e. included in"off-target" group, * never been randomized because, the enrollment in the off target group was completed.
• Aged ≥6 years old;
• Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to localregulations);
• Subjects must be willing to use adequate contraception: * Contraceptive methods must since the previous GIVINOSTAT study through 3 months after the last dose of study drug, and include the following: * True abstinence (absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the subject. * Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. * Condom with spermicide and the female partner must use an acceptable method of contraception, such as an oral, * transdermal, injectable or implanted steroid-basedcontraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such asfor example cervical cap with spermicide jelly.
Exclusion Criteria:
• Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to be enrolled in this study (e.g., growth hormone); Vitamin D, calcium, and any other supplements will be allowed;
• Use of any current investigational drug other than Givinostat;
• Have presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results;
• Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD;
• Have platelets count, White Blood Cell and Hemoglobin at screening \< Lower Limit of Normal (LLN)\* (for abnormal screening laboratory test results (\
• Have inadequate renal function, as defined by serum Cystatin C \>2 x the upper limit of normal (ULN) at screening visit\*. If the value is \>2 x ULN, the serum Cystatin C will be repeated once; if the repeated test result is still \>2 x ULN, the subject should be excluded);
• Have heart failure (New York Heart Association Class III or IV)
• Have a current liver disease or impairment, including but not limited to an elevated total bilirubin\* (i.e. \> 1.5 x ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert's;
• Have a baseline QTcF \>450 msec, (as the mean of 3 consecutive readings 5 minutes apart) or history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome);
• Have a psychiatric illness/social situation rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures.
• Have any hypersensitivity to the components of study medication;
• Have a sorbitol intolerance or sorbitol malabsorption or have the hereditary form of fructose intolerance. * the Investigators to evaluate these exclusion criteria can use the laboratory results obtained within 5 months from V1, to allow the continuity of the treatment. It is worth noting, as soon as the site will receive the laboratory results done in screening/baseline (Visit 1) visit they will check the GIVINOSTAT dose and modify it as per protocol safety rules and/or dosage modifications rules.
DRUG: Givinostat
Duchenne Muscular Dystrophy
Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA) (RESTORE)
Novartis Gene Therapies - novartis.email@novartis.com
Johnson, Nicholas, E
NCT04174157
HM20015046
Inclusion Criteria:
* Patients treated with OAV-101 with a genetically confirmed diagnosis of SMA regardless of the date of diagnosis.
* Appropriate consent/assent has been obtained for participation in the registry
Exclusion Criteria:
• Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat SMA. Note: Patients who are participating in a Compassionate Use Program (CUP) for OAV-101 (Zolgensma) such as a Managed Access Program (MAP), an Expanded Access Program (EAP), Single Patient Investigational New Drug (IND) (SPI) or Named Patient Program (NPP) are eligible to enroll in the registry regardless of the date of a genetic or clinical diagnosis of SMA.
OTHER: Prospective observational registry, DRUG: Zolgensma
Spinal Muscular Atrophy (SMA)
Post Approval Study for Treatment of Drug-resistant Adult and Pediatric Primary FSGS Using the LIPOSORBER® LA-15 System (FSGSALLAGE)
Ayaka Kitamura - Ayaka.Kitamura1@kaneka.co.jp
NCT04065438
Inclusion Criteria:
A patient is deemed suitable for inclusion in the study if the patient has nephrotic syndrome associated with primary FSGS when:
• Standard treatment options, including corticosteroid and/or calcineurin inhibitors, are unsuccessful or not well tolerated and the patient's glomerular filtration rate (GFR) ≥ 45 ml/min/1.73 m2.
or
• The patient is post renal transplantation.
Exclusion Criteria:
General Exclusion Criteria
• Patient is greater than 75 years of age at the start of the treatment period or less than 22
• The patient is unwilling or unable to sign and date the informed consent
• Pregnant, lactating, or planning to become pregnant prior to completing the study (Note: The safety of the use of LIPOSORBER® in pregnant women has not been studied. There may be unknown risks to an embryo/fetus. Sexually active women of childbearing potential should avoid pregnancy during the use of the LIPOSORBER device and throughout the study duration.)
• Unable or unwilling to comply with the follow-up schedule
• Simultaneously participating in another investigational drug or device study
• Body weight \< 15 kg (33.1 lbs) Medical Exclusion Criteria
• Currently being administered ACE inhibitors that cannot be withheld for at least 24 hours prior to each apheresis treatment (Note: The time period to withhold ACE inhibitors should be prolonged, if determined by the treating physician, considering each individual's renal function and the biological half-life of the ACE-inhibitor currently in use.)
• Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., ARBs) that cannot be withheld on the day of apheresis until after the procedure
• Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis
• Hypersensitivity to dextran sulfate, heparin, or ethylene oxide
• Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications
• Extracorporeal circulation therapy with LIPOSORBER® LA-15 System cannot be tolerated due to severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute apoplexy, severe uncontrollable hypertension, or severe uncontrollable hypotension Note: Severe uncontrollable hypotension/hypertension indicates the cases with systolic and/or diastolic blood pressure ≤ 5th percentile for age, gender, and height.
• Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease
• Functional thyroid disease or liver abnormalities
• Unresolved systemic or local infection that could affect the clinical study outcomes
DEVICE: LIPOSORBER® LA-15
Focal Segmental Glomerulosclerosis
FSGS, Liposorber