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387 Study Matches

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Enzastaurin Added to Temozolomide During and Following Radiation Therapy in Newly Diagnosed Glioblastoma Patients Who Possess the Novel Genomic Biomarker DGM1

To assess whether there is superiority of overall survival (OS) when enzastaurin rather than placebo is added to the regimen of temozolomide with radiation therapy followed by temozolomide for the treatment of patients with newly diagnosed glioblastoma in DGM1 biomarker-positive patients, regardless of MGMT methylation status.

Elizabeth Neil
Phase III
This study is NOT accepting healthy volunteers
NCT03776071
STUDY00011956
Glioblastoma
Clinics and Surgery Center (CSC)
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of
Evinacumab in Patients with Severe Hypertriglyceridemia for the Prevention of Recurrent Acute
Pancreatitis

The primary objective of the study is to determine the proportion of patients with TG >880 mg/dL, without FCS due to LoF mutations in LPL, and a history of HTG-associated AP who experience a recurrent episode of AP after treatment with evinacumab versus placebo.

Daniel Duprez
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04863014
STUDY00013985
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Key
Inclusion Criteria:

• Adults without FCS due to LPL loss of function mutations
• Documented history of 1 HTG-associated AP episode within 24 months of screening
• Fasting serum TG value >880 mg/dL (10 mmol/L) or >500 mg/dL (5.6mmol/L) determined during the screening period as described in the protocol
• Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study
• Body mass index ≥18.0 and ≤45.0 kg/m2
• Compliance with a stable diet and exercise regimen at screening and willingness to continue the diet through the end of the study Key
Exclusion Criteria:

• Hospitalization for AP within 4 weeks of screening
• Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol
• Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol
• Use of any medication or nutraceutical known to alter serum lipids which has not been part of a stable therapeutic regimen for at least 8 weeks, and there are no plans to change the regimen during the study
• Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
• Has received a COVID-19 vaccination within 1-week of planned start medication or for which the planned COVID-19 vaccination would not be completed 1-week prior to start of the study Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Drug: evinacumab, Other: Placebo
Heart & Vascular, Hypertriglyceridemia
Severe Hypertriglyceridemia (HTG), Recurrent Acute Pancreatitis, Clinics and Surgery Center (CSC)
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MT2018-19: COG ANBL1531 - A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children with Newly Diagnosed High-Risk Neuroblastoma (NBL) (IND# 134379)

This partially randomized phase III trial studies iobenguane I-131 or ALK Inhibitor Therapy and standard therapy in treating younger patients (365 days to 30 years of age) with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma.

Emily Greengard
All
365 Days to 30 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03126916
STUDY00003568
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Inclusion Criteria:

• Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
• Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• Age > 547 days regardless of biologic features
• Patients with INRG stage MS disease with MYCN amplification
• Patients with INRG stage L2 disease with MYCN amplification
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
• Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
• Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
• 1 to < 2 years: male = 0.6; female = 0.6
• 2 to < 6 years: male = 0.8; female = 0.8
• 6 to < 10 years: male = 1; female = 1
• 10 to < 13 years: male = 1.2; female = 1.2
• 13 to < 16 years: male = 1.5; female = 1.4
• >= 16 years: male = 1.7; female = 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:

• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
• Patients with bone marrow failure syndromes
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
• 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
Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Busulfan, Drug: Carboplatin, Drug: Cisplatin, Drug: Crizotinib, Drug: Cyclophosphamide, Drug: Dexrazoxane Hydrochloride, Biological: Dinutuximab, Drug: Doxorubicin Hydrochloride, Drug: Etoposide Phosphate, Radiation: External Beam Radiation Therapy, Radiation: Iobenguane I-131, Drug: Isotretinoin, Drug: Melphalan Hydrochloride, Biological: Sargramostim, Procedure: Therapeutic Conventional Surgery, Drug: Thiotepa, Drug: Topotecan Hydrochloride, Drug: Vincristine Sulfate
Ganglioneuroblastoma, INRG Stage L2, INRG Stage M, INRG Stage MS, Neuroblastoma
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Phase II Randomized, Intervention Versus Non-Intervention, Multi-Center Study of the Effects of Thyroid Hormone (T3) on Extravascular Lung Water (EVLW) in Subjects with Acute Respiratory Distress Syndrome (ARDS) (ARDS+T3)

Study objective: To determine the safety and tolerability of Thyroid Hormone (T3) delivery into the lungs of Acute Respiratory Distress Syndrome (ARDS) patients, and to measure the effect of T3 on extravascular lung water in ARDS patients.

Ronald Reilkoff
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04115514
STUDY00007410
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Inclusion Criteria:
Clinical diagnosis of ARDS:
• Chest x-ray: bilateral pulmonary infiltrates
• Hypoxemia: PaO2:FIO2 ratio <200
• Volume status: wedge and CVP<18 Main inclusion criteria:
• Adults (≥18 years of age), non-pregnant
• On mechanical ventilatory support
Exclusion Criteria:

• Inadequate medical history for determining inclusion/exclusion criteria, as determined by the Principal Investigator and/or Sub-Investigators.
• Unlikely to complete the protocol with clinic follow-up after discharge, as determined by the Principal Investigator and/or Sub-Investigators or hospice status.
• Active drug/alcohol use with positive drug screen or alcohol level on admission.
• Prior history of thyroid cancer or hyperthyroidism, per thorough patient/family interviews, review of past medical history, medication list, laboratory test.
• Prior history of cardiovascular disease including:
• Hypertensive crisis in the past 3 months (systolic >200, or diastolic >120 mmHg),
• Sustained ventricular arrhythmia in the past 3 months (duration > 30 seconds)
• Coronary artery disease (documented >50% occlusion in any coronary vessel)
• Cardiac-related angina pectoris (> 2 episodes in the past 3 months)
• Myocardial infarction with ischemia on ECG (i.e., new ST-elevation/depression of >1mm in contiguous leads), or positive cardiac enzymes (Ratio of CK-MB: Total CK > 3.5).
• Peripheral vascular disease (documented >50% occlusion in any peripheral vessel).
• Moderate or severe ischemic/non-ischemic cardiomyopathy (documented ejection fraction < 40%).
• Decompensated or symptomatic heart failure (i.e., hospitalized for CHF exacerbation, or a change in CHF medications within two weeks prior)
• Currently pregnant or breastfeeding.
• Currently taking tricyclic antidepressants, glycosides, ketamine, or vasopressors with ongoing evidence of myocardial ischemia.
• Known allergy to study drug.
Drug: Liothyronine Sodium (T3) (modified formulation)
ARDS, Human, Lung, Wet, Thyroid, Pulmonary Edema, Lung Inflammation
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An Open-Label, Single-Arm, Multicenter Study of Intracerebral Administration of Adeno-Associated Viral Vectors Serotype rh10 Carrying the Human N sulfoglucosamine sulfohydrolase (SGSH) cDNA for the Treatment of Mucopolysaccharidosis Type IIIA (AAVance)

Chester Whitley, MD, PhD
All
6 Months and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03612869
STUDY00004084
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Inclusion Criteria:

• Documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
• Cognitive DQ score on BSID-III: 50% and above
Exclusion Criteria:

• Homozygous for the S298P mutation or non-classical severe form of MPS IIIA, based on investigator's judgement.
• Participation in another gene or cell therapy clinical trial.
• Past use of SGSH enzyme replacement therapy for a period exceeding 3 months. A washout period of at least 2 months is required prior to screening.
• Current participation in a clinical trial of another investigational medicinal product.
• History of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following surgery.
• Any condition that would contraindicate treatment with immunosuppressants such as tacrolimus, mycophenolate mofetil or steroids.
Drug: LYS-SAF302
Mucopolysaccharidosis Type IIIA
MPS IIIA, Sanfilippo syndrome Type A, Mucopolysaccharidosis Type IIIA, Lysosomal Storage Disease
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MT2019-40: A Phase I, Open-Label, Multicenter Study of FT596 as a Monotherapy and in Combination with Rituximab or Obinutuzumab in Subjects with Relapsed/Refractory B-cell Lymphoma and Chronic Lymphocytic Leukemia

This study is designed to determine the recommended Phase II dose (RP2D), as well as evaluate the safety and efficacy for FT596 as monotherapy and in combination with rituximab or obinutuzumab in patients with relapsed/refractory B-cell Lymphoma and Chronic Lymphocytic Leukemia.

Veronika Bachanova, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04245722
STUDY00008387
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Inclusion Criteria:
Diagnosis of B-cell lymphoma or CLL as described below: B-Cell Lymphoma:
• Histologically documented lymphomas expected to express CD19 and CD20
• Relapsed/refractory disease following prior systemic immunochemotherapy regimen Chronic Lymphocytic Leukemia (CLL):
• Diagnosis of CLL per iwCLL guidelines
• Relapsed/refractory disease following at least two prior systemic treatment regimens ALL SUBJECTS:
• Capable of giving signed informed consent
• Age ≥ 18 years old
• Stated willingness to comply with study procedures and duration
• Contraceptive use for women and men as defined in the protocol Key
Exclusion Criteria:
ALL SUBJECTS:
• Females who are pregnant or breastfeeding
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2
• Body weight <50 kg
• Evidence of insufficient organ function
• Receipt therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1
• Currently receiving or likely to require systemic immunosuppressive therapy
• Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy
• Receipt of an allograft organ transplant
• Known active central nervous system (CNS) involvement by malignancy
• Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Clinically significant cardiovascular disease
• Known HIV infection
• Known active Hepatitis B (HBV) or Hepatitis C (HCV) infection
• Live vaccine <6 weeks prior to start of lympho-conditioning
• Known allergy to albumin (human) or DMSO
Drug: FT596, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Rituximab, Drug: Obinutuzumab
Lymphoma, B-Cell, Chronic Lymphocytic Leukemia
Lymphoma, Leukemia, Clinics and Surgery Center (CSC)
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A Phase 3, Open-label, Randomized Study of Nivolumab Combined with Ipilimumab, or with Standard of Care Chemotherapy, versus Standard of Care Chemotherapy in participants with Previously Untreated Unresectable or Metastatic Urothelial Cancer

This is a randomized, open-label, Phase 3 study comparing combination therapy of nivolumab plus ipilimumab administered every 3 weeks for up to 4 doses, followed by nivolumab monotherapy administered every 4 weeks, versus the standard of care in participants with previously untreated unresectable or metastatic urothelial cancer. In addition, a substudy of treatment with nivolumab 360mg in combination with SoC every 3 weeks for up to 6 cycles followed by nivolumab monotherapy versus SoC alone will be evaluated in cisplatin-eligible participants with previously untreated unresectable or metastatic urothelial cancer.

Gautam Jha
Phase III
This study is NOT accepting healthy volunteers
NCT03036098
STUDY00001304
Urothelial Cancer
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare the Efficacy and Safety of Sotatercept Versus Placebo When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH

The objective of this study is to evaluate the efficacy and safety of sotatercept treatment (plus background P AH therapy) versus placebo (plus background PAH therapy) at 24 weeks in adults with PAH.

Thenappan Thenappan
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04576988
STUDY00012824
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Inclusion Criteria:

• Age ≥ 18 years
• Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of WHO pulmonary arterial hypertension (PAH) Group 1 in any of the following subtypes:
• Idiopathic PAH
• Heritable PAH
• Drug/toxin-induced PAH
• PAH associated with connective tissue disease
• PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
• Symptomatic PAH classified as WHO Functional Class II or III
• Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of ≥ 5 Wood units (WU) and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure of ≤ 15 mmHg.
• On stable doses of background PAH therapy and diuretics (i.e., patient-specific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice.
• 6MWD ≥ 150 and ≤ 500 m repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value)
• Females of childbearing potential must:
• Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; she must agree to ongoing urine or serum pregnancy testing during the study and until 8 weeks after the last dose of the study drug
• If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment
• Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment
• Male participants must:
• Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
• Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment
• Ability to adhere to study visit schedule and understand and comply with all protocol requirements
• Ability to understand and provide written informed consent Key
Exclusion Criteria:

• Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
• Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension. Exclusions in PAH Group I should also include schistosomiasis APAH and pulmonary veno occlusive disease
• Hemoglobin (Hgb) at screening above gender-specific upper limit of normal (ULN), per local laboratory test
• Baseline platelet count < 50,000/mm3 (< 50.0 x 109/L) at screening
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 100 mmHg during screening visit after a period of rest
• Baseline systolic BP < 90 mmHg at screening
• Pregnant or breastfeeding women
• Any of the following clinical laboratory values at the screening visit:
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/m2 (as defined by MDRD equation)
• Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels > 3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome)
• Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
• Prior exposure to sotatercept (ACE-011) or luspatercept (ACE 536) and/or excipients or known allergic reaction to either one
• Have full or partial pneumonectomy
• Pulmonary function test (PFT) values of forced vital capacity (FVC) < 60% predicted at the screening visit or within 6 months prior to the screening visit. If PFT is not available, a chest CT scan showing more than mild interstitial lung disease (ILD) performed at the screening visit or 1 year prior to it.
• Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the screening visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
• History of more than mild obstructive sleep apnea that is untreated
• Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A-C)
• History of restrictive, constrictive or congestive cardiomyopathy
• History of atrial septostomy within 180 days prior to the screening visit
• Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 500 ms during the screening period
• Personal or family history of long QT syndrome (LQTS) or sudden cardiac death
• Left ventricular ejection fraction < 45% on historical echocardiogram within 6 months prior to the screening visit
• Any symptomatic coronary disease events within 6 months (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months of the screening visit. Note: Anginal pain can be ignored as an exclusion criterion if coronary angiography shows no obstructions.
• Cerebrovascular accident within 3 months prior to the screening visit
• Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment
• Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit
Drug: Sotatercept, Drug: Placebo
Pulmonary Arterial Hypertension
Pulmonary, Hypertension, sotatercept, Clinics and Surgery Center (CSC)
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A Phase 3, Randomized, Placebo-controlled, Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD) (PERFECT)

The primary objective of this study is to demonstrate the efficacy of inhaled treprostinil compared to placebo in improving exercise ability as measured by change from baseline in 6MWD following 12 weeks of active treatment in subjects with PH-COPD.

Thenappan Thenappan
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03496623
STUDY00012487
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Inclusion Criteria:
Participants who meet the following criteria may be included in the study:
• Participant voluntarily gives informed consent to participate in the study.
• Males and females 18 years of age and above at the time of informed consent.
• Women of childbearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, [<1% per year], such as approved hormonal contraceptives, barrier methods [such as condom or diaphragm] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. Participants must have a negative pregnancy test at the Screening Visit 1 (urine [prior to the first dose of study medication] and serum) and Baseline Visit (Study Week 1) (urine).
• Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug.
• Diagnosis of PH-COPD (World Heath Organization [WHO] Group 3).
• Clinical diagnosis of COPD will be made using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria (GOLD Criteria 2020) and spirometry with the following documented parameters measured during Screening Visit 1 (prior to start of low-dose inhaled treprostinil):
• Forced expiratory volume in 1 second (FEV1) <80% predicted
• FEV1/Forced vital capacity (FVC) <70
• The participant has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 liters (L)/min oxygen supplementation by any mode of delivery during Screening Visit 1.
• During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters.
• Have a right heart catheterization (RHC) performed during Screening Visit 1. (A previous RHC obtained within 12 months prior to the start of Screening Visit 1 is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and a repeat RHC is not required.) The following parameters must be documented for eligibility:
• Pulmonary vascular resistance (PVR) greater than or equal to 4 Wood units
• A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 millimeters of mercury (mmHg)
• A Pulmonary artery pressure mean (PAPm) of greater than or equal to 30 mmHg
• Participants must be on a stable and optimized dose of chronic COPD medications for greater than or equal to 30 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period.
• In the opinion of the Investigator, the participant can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
Exclusion Criteria:
The following will exclude participants from the study:
• The participant has a diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD. This would include, but is not limited to, chronic thromboembolic PH or acute/recent deep vein thrombosis or pulmonary embolism, untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma or systemic lupus erythematosus), sarcoidosis, human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.
• Based on chest computed tomography (CT) imaging during Screening Visit 1, the participant has a confirmed diagnosis of WHO Group 3 PH, other than COPD, such as idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease or interstitial lung disease. A previous chest CT scan performed within the 6 months prior to the start of Screening Visit 1 is also acceptable, and a repeat assessment is not required. A redacted CT scan report (from Screening Visit 1 or dated within prior 6 months) should be provided to the Medical Monitor with the Pre-Baseline Review Form to confirm eligibility.
• The participant has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (that is, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) at Screening Visit 1 and thereafter, except if received for acute vasoreactivity testing.
• The participant has a previous diagnosis of homozygous alpha-1 antitrypsin deficiency.
• The participant has any prior intolerance to inhaled prostanoid therapy.
• Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization).
• Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).
• The participant has evidence of clinically significant left-sided heart disease (including but not limited to left ventricular ejection fraction <40%, left ventricular hypertrophy,) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease. Note: Participants with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor Medical Monitor is needed.
• Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection 60 days prior to start of Screening Visit 1 through the Baseline Visit. This is defined as worsening of respiratory symptoms that required treatment with corticosteroids and/or antibiotics.
• Initiation of pulmonary rehabilitation within 12 weeks prior to start of Screening Visit 1 or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the study Treatment Period.
• The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
• The participant has any musculoskeletal disorder (severe arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or any other condition that would likely be the primary limitation to ambulation.
• Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1.
• Any other clinically significant illness or abnormal laboratory value(s) measured during the Screening Period that, in the opinion of the Investigator, might adversely affect the interpretation of the study data or safety of the participant.
Drug: Inhaled treprostinil solution, Drug: Placebo solution
Pulmonary Hypertension, Chronic Obstructive Pulmonary Disease
Pulmonary Hypertension, COPD, Inhaled Treprostinil, 6-Minute Walk Test, Tyvaso, Clinics and Surgery Center (CSC)
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A Phase 3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Females 16-40 Years of Age (mRNA-1647-P301)

This is a Phase 3, randomized, observer-blinded, placebo-controlled study in healthy participants 16 to 40 years of age. The primary efficacy objective is to demonstrate vaccine effect of mRNA-1647 against primary cytomegalovirus (CMV) infection in female participants who are CMV-seronegative at enrollment.

Mark Schleiss
Not specified
Phase III
This study is also accepting healthy volunteers
NCT05085366
STUDY00013943
Cytomegalovirus Infection, Infectious Diseases, Prevention & Wellness, Women's Health
CMV, Cytomegalovirus, Cytomegalovirus (CMV), Cytomegalovirus Congenital, Cytomegalovirus Infections, Cytomegalovirus Vaccine, DNA Virus Infections, Healthy Participants 16 to 40 Years of Age, Infection Viral, Messenger RNA, Moderna, Vaccine, Virus Diseases, mRNA-1647
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A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK PathwayMutant Acute Lymphoblastic Leukemia Protocol Number: AALL1521/INCB 18424-269

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-ALL. Subjects with de novo B-ALL, aged 1 to 21 years at the time of diagnosis, will be evaluated for genetic eligibility during the Induction phase of a 4-drug regimen (modified augmented Berlin-Frankfurt-Münster (aBFM) or equivalent).

Peter Gordon
All
1 Year to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT02723994
1609M94601
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Inclusion Criteria:

• Eligible for study when participant is 1 year to 21 years at the time of diagnosis
• Eligible Ages in Australia and Canada; 2 years to 21 years
• De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
• Age ≥ 10 years
• White blood cell (WBC) ≥ 50 × 10^3/μL
• CNS3 leukemia at diagnosis
• Systemic steroid pretreatment without presteroid WBC documentation
• Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent CAP/CLIA-certified laboratories approved by the medical monitor:
• CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
• CRLF2 rearrangement* without JAK mutation
• Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status*† as determined by a COG ALL Reference Laboratory
• Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or its successor study, or as per the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
• Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation
Exclusion Criteria:

• Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
• Trisomy 21 (Down syndrome)
• BCR-ABL1-rearranged (Ph+) ALL
• Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2
• Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age
• Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
• History or evidence of cirrhosis
• Platelet count < 75 × 10^3/μL
• Absolute neutrophil count (ANC) < 750/μL
• Positive screen for hepatitis B or C
• Known human immunodeficiency virus infection
Drug: Ruxolitinib, Drug: Asparaginase Erwinia Chrysanthemi, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisone, Drug: Thioguanine, Drug: Vincristine Sulfate
Leukemia
B-cell acute lymphoblastic leukemia (ALL), pediatric, multi-agent chemotherapy, JAK inhibitor
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Phase 1/2 Study to Evaluate Palbociclib (IBRANCE?) in Combination With Irinotecan and Temozolomide and/or in Combination with Topotecan and Cyclophosphamide in Pediatric Patients With Recurrent or Refractory Solid Tumors Protocol No.: ADVL1921/A5481092

This is a Phase 1/2 multicenter, open-label study to evaluate palbociclib in combination with either irinotecan (IRN) and temozolomide (TMZ) or topotecan (TOPO) and cyclophosphamide (CTX) chemotherapy in children, adolescents and young adults with recurrent or refractory solid tumors. The study consists of a non- randomized Phase 1 portion for recurrent or refractory solid tumors followed by potential non- randomized tumor specific cohort(s) and a randomized, Phase 2 portion for recurrent or refractory EWS.

Emily Greengard
All
2 Years to 20 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03709680
STUDY00007068
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Inclusion:
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma. Histopathology confirmation of EWSR1-ETS or FUS-ETS rearrangement is required or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or refractory disease with no known bone marrow metastases and at least evaluable disease.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
• Evidence of a personally signed and dated informed consent document indicating that the patient or a legally acceptable representative/parent(s)/legal guardian of minors, has been informed of all pertinent aspects of the study. Minor study patients also must provide age appropriate assent according to the local guidelines, where applicable.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 :prior treatment with a CDK4/6 inhibitor or prior treatment with an IRN and/or TMZ-containing regimen.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Prior growth factors (including filgrastim) within 7 days before study entry or PEG-filgrastim within 14 days before study entry.
• Radiation therapy within 14 days before study entry.
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Previous high dose chemotherapy requiring stem cell rescue within 90 days or persistent AE >Grade 1.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.Phase 2 portion patients with bone marrow involvement are excluded.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
• Other severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 after the last dose of investigational product.
Drug: Palbociclib, Drug: Temozolomide, Drug: Irinotecan, Drug: Topotecan, Drug: Cyclophosphamide
Ewing Sarcoma, Solid Tumors, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), neuroblastoma (NBL), Brain tumor
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A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, a rAAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects with Fabry Disease

The proposed study uses a recombinant AAV2/6 vector encoding the cDNA for human α-Gal A (ST-920). The α-Gal A produced by this cDNA has an identical amino acid sequence to the native enzyme, and also to Fabrazyme® (agalsidase beta or equivalent), a clinically approved recombinant protein product. The ST-920 construct encodes a liver-specific promoter, the human α-1-antitrypsin (hAAT) promoter and includes liver-specific regulatory elements. In addition, rAAV2/6 exhibits liver tropism thus providing the potential for long-term hepatic production of α-Gal A in Fabry disease subjects. Studies of ST-920 in a Fabry disease mouse model administered rAAV2/6 encoding hGLA cDNA by intravenous (IV) injection show generation of therapeutic circulating levels of α-Gal A. The one-time treatment with ST-920 minimizes the risk of infusion--related reactions. The goal of ST-920 is to provide stable, long-term production of α-Gal A at therapeutic levels in subjects with Fabry disease. The constant production of α-Gal A in humans should, importantly, enable reduction and potentially clearance of Fabry disease substrates Gb3 and lyso-Gb3.

Chester Whitley, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04046224
STUDY00007094
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Inclusion Criteria:

• ≥ 18 years of age
• Documented diagnosis of Fabry disease
• One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma
Exclusion Criteria:

• Known to be unresponsive to ERT
• Neutralizing antibodies to AAV2/6
• Currently receiving migalastat (Galafold™)
• eGFR ≤ 40 ml/min/1.73m2
• New York Heart Association Class III or higher
• Active infection with hepatitis A, B or C, HIV or TB
• History of liver disease such as secondary steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, cholangitis or biliary disease within 6 months of informed consent; except for Gilbert's syndrome
• Elevated circulating serum AFP
• Recent or recurrent hypersensitivity response to ERT within previous 6 months
• Current or history of systemic (IV or oral) immunomodulatory agents, or biologics or steroid use in the past 6 months (topical treatment and inhaled allowed).
• Contraindication to use of corticosteroids
• History of malignancy except for non-melanoma skin cancer
• Recent history of alcohol or substance abuse
• Participation in prior investigational interventional drug or medical device study within previous 3 months
• Prior treatment with a gene therapy product
• Known hypersensitivity to components of ST-920 formulation
• Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study including but not limited to risk of COVID-19 infection
Biological: ST-920
Fabry Disease
Sangamo, Rare, Lysosomal Storage Disease, Gene Therapy
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MT2020-24: A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9 Engineered T Cells (CTX110) in Subjects With Relapsed or Refractory B Cell Malignancies

Primary objective, Part A (dose escalation): To assess the safety of escalating doses of CTX110 in subjects with relapsed or refractory B cell malignancies to determine the recommended Part B dose Primary objective, Part B (cohort expansion): To assess the efficacy of CTX110 in subjects with relapsed or refractory B cell malignancies, as measured by objective response rate (ORR)

Joseph Maakaron
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04035434
STUDY00010648
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Key
Inclusion Criteria:

• For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
• Refractory or relapsed non-Hodgkin lymphoma, as evidenced by 2 or more lines of prior therapy, or histologically confirmed B cell ALL, refractory or relapsed.
• Eastern Cooperative Oncology Group performance status 0 or 1.
• Adequate renal, liver, cardiac and pulmonary organ function
• Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX110 infusion.
• Agree to participate in an additional long-term follow-up study after completion of this study. Key
Exclusion Criteria:

• Treatment with any gene therapy or genetically modified cell therapy, including CAR T cells.
• For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
• History of central nervous system (CNS) involvement by malignancy
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives.
• Active HIV, hepatitis B virus or hepatitis C virus infection.
• Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years.
• For NHL patients: Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of enrollment.
• Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
• Women who are pregnant or breastfeeding.
Biological: CTX110
B-cell Malignancy, Non-Hodgkin Lymphoma, B-cell Lymphoma, Adult B Cell ALL
Clinics and Surgery Center (CSC), CAR T, Non-Hodgkin Lymphoma, NHL, Lymphoma, Allogeneic, Leukemia
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A Phase 1/2 Study of the Oral RET Inhibitor LOXO-292 in Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors; Protocol Number: LOXO-RET-18036 (J2G-OX-JZJJ) (LIBRETTO-121)

This is an open-label, multi-center, Phase 1/2 study of oral LOXO-292 in pediatric patients with an activating RET alteration and an advanced solid or primary CNS tumor.

Emily Greengard
All
6 Months to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03899792
STUDY00008874
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Inclusion Criteria:

• Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Measurable or non-measurable disease
• Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
• Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
• Adequate hematologic, hepatic and renal function.
• Ability to receive study drug therapy orally or via gastric access
• Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion Criteria:

• Major surgery within two weeks prior to planned start of LOXO-292
• Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
• Clinically significant active malabsorption syndrome
• Pregnancy or lactation
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
• Uncontrolled symptomatic hypercalcemia or hypocalcemia
• Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
• Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])
Drug: LOXO-292
Medullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma, Papillary Thyroid Cancer, Soft Tissue Sarcoma
Loxo, LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Adenoma, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Colonic Neoplasms, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, Soft tissue sarcoma, Infantile Myofibromatosis, Infantile Fibrosarcoma
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A Phase II, Open Label, Two Arm Study of Therapeutic Iobenguane (131I) as Single Agent or in Combination with Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects (OPTIMUM Trial) Protocol Number: MIBG 2014-01 (OPTIMUM)

This will be a Phase II, two-arm, nonrandomized, non-comparative, open-label study in participants ≥ 1 year of age with iobenguane avid, recurrent or progressive high-risk neuroblastoma. Participants not eligible for vorinostat treatment may receive 131I-MIBG as monotherapy.

Emily Greengard
All
1 Year and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03561259
STUDY00005792
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Inclusion Criteria:

• Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment.
• May have had prior 131I-MIBG therapy, provided:
• It has been at least 6 months from the date of last 131I-MIBG ;
• Response was other than progressive disease on first restaging after 131I-MIBG ;
• Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents;
• Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
• All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or
• any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion.
• any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator.
• Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
• If a male, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.
• If a female of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study.
• Age at study entry ≥1 year.
• Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week.
• Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
• An absolute neutrophil count ≥750/μL without growth factor for 5 days.
• Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L).
• Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
• Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline).
• Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
• Full recovery from the toxic effects of any prior therapy.
• Coagulation Function:
• International Normalized Ratio (INR) < 1.5
• Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.
Exclusion Criteria:

• Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy.
• Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
• Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible.
• Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. Subjects whose only site(s) of disease have been radiated are eligible as long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum of 12 weeks prior to study enrollment is required following prior large field radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
• History of total body irradiation.
• Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either by creatinine clearance or radioisotope direct measurement or by calculation with the Schwartz formula
• Subjects who are on hemodialysis.
• Pregnancy or breastfeeding.
• Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry).
• Clinically important cardiac, pulmonary, and hepatic impairment.
• Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
• Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry.
• Since vorinostat may prolong the QT interval, patients must not be receiving other medications known to prolong the QT interval at the time of study entry . Pentamidine must not have been received within 1 week of study enrollment.
• Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter.
• Patients who are receiving Coumadin.
Drug: 131I-MIBG, Drug: 131-MIBG + Vorinostat
Neuroblastoma, Neuroectodermal Tumors, Neoplasms
Iobenguane Avid High-risk Neuroblastoma, 3-Iodobenzylguanidine, Radiopharmaceutical
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EA5163/S1709 INSIGNA: A Randomized, Phase III Study of Firstline Immunotherapy alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature driven Analysis

Phase III
This study is NOT accepting healthy volunteers
NCT03793179
0123456789
Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
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A randomized, controlled, multi-center, safety and efficacy study of FCR001 cell-based therapy relative to a tacrolimus and mycophenolate-based regimen in de novo living donor renal transplant recipients, and safety in FCR001 donors (FREEDOM-1)

The purpose of this study is to assess the safety, efficacy and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation, relative to a standard-of-care control regimen including tacrolimus, mycophenolate, antibody induction, and corticosteroids. FCR001 is a novel, cryopreserved allogeneic somatic cell therapy, derived from mobilized peripheral blood mononuclear cells from the same donor as the allograft, and containing hematopoietic progenitor cells, facilitating cells and αβ T cells. The rationale is to establish durable chimerism and donor-specific tolerance in the recipient enabling freedom from chronic IS and its associated toxicities.

Erik Finger
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03995901
STUDY00006880
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Inclusion Criteria:

• Written informed consent must be obtained, from recipients and donors, before any assessment is performed on the respective subject.
• Recipient age ≥18 years.
• Donor age ≥18 and ≤60 years
• Recipients of a first kidney transplant from a living unrelated or non- human leukocyte antigen (HLA) identical living related donor.
• Donor willing to undergo mobilization, apheresis and 12-month safety follow-up. Donor and Recipient: COVID-19 nucleic acid test (NAT) (e.g., SARS-CoV-2 RT-PCR) negative.
• Must be willing and able to comply with protocol-required visit schedule and visit requirements. Recipient and Donor
Exclusion Criteria:

• Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent.
• Recipient or donor with history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• Recipient and donor who are identical twins.
• Recipient or donor who is a pregnant or nursing (lactating) woman.
• Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome) of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Recipient or donor with known bone marrow aplasia. Recipient-only
Exclusion Criteria:

• Multi-organ or cell transplant recipient.
• Panel reactive antibodies (calculated panel reactive antibody>20% by Flow/Luminex).
• Recipient is blood type ABO incompatible or has positive crossmatch (Flow/Luminex) vs. donor.
• Presence of donor-specific antibodies (DSA) (positive result) at any time pre-transplant.
• Recipient who is human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) positive.
• Recipient with systemic infection, current or within the 2 weeks prior to conditioning; or history of recurrent infection (eg, polycystic liver/kidney disease, unless native kidneys removed at time of transplant).
• Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (eg, autoimmune disease, asthma) throughout the course of the study.
• Recipient who had a live attenuated vaccine administered within 2 months of planned transplant surgery.
• Recipient with a BMI < 18 or > 35 kg/m2.
• Recipient requiring systemic anticoagulation, (eg, for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted which would preclude renal biopsy.
• Recipient with contraindication to total body irradiation (TBI) according to local radiologist, eg, previous radiation therapy at a dose which would preclude TBI, inadequate pulmonary function.
• Recipient with autologous or allogeneic hematopoietic progenitor cell transplant prior to signing informed consent.
• All recipient women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who do not agree to using highly effective methods of contraception during dosing of study treatment.
• Sexually active male control recipient must use a condom during intercourse throughout the study and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of drugs via seminal fluid. FRC001 recipient this requirement may be lifted at 6 weeks after MMF and tacrolimus have been discontinued. Donor-only
Exclusion Criteria:

• Biologically unrelated female donor transplant to male recipient.
• Donor tested positive for Zika virus (ZIKV) infection. Zika infection is excluded by negative nucleic acid testing result on either serum or urine PLUS a negative Zika IgM. Only donors with the following risk factors must be tested:
• Medical diagnosis of ZIKV in the past 6 months.
• Residence in, or travel to, an area with an increased risk for ZIKV transmission within the past 6 months.
• Sex within the past 6 months with a person who has either of the risk factors listed in items (a) or (b), above.
Biological: FCR001
Transplanted Organ Rejection
Kidney Transplant, Stem cell therapy, Anti-rejection medications, Living donor kidney transplant, Immune tolerance
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CB8025-32048: RESPONSE: A Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

The purpose of this study is to determine if an investigational drug, seladelpar, is safe and effective in treating patients with PBC compared to placebo. This will be done by looking at how the drug affects PBC, specifically looking at changes in laboratory parameters, such as alkaline phosphatase (ALP), bilirubin, gamma-glutamyl transferase (GGT), and other laboratory tests that are used to monitor the severity of PBC and its prognosis. This is an international, multicenter evaluation of seladelpar in a randomized, double-blind, placebo-controlled, parallel-group study in patients with PBC. Approximately 180 subjects will be randomized in 2:1 ratio (seladelpar:placebo) across approximately 150 sites worldwide.

John Lake
All
18 Years to 75 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04620733
STUDY00012441
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Inclusion Criteria:

• Must have given written informed consent (signed and dated) and any authorizations required by local law
• 18 to 75 years old (inclusive)
• Male or female with a definitive diagnosis of PBC
• UDCA for the past 12 months (stable dose for >3 months prior to screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to screening)
• Laboratory parameters measured by the Central Laboratory at screening:
• ALP ≥1.67× ULN
• Aspartate aminotransferase (AST) ≤3× ULN
• ALT ≤3× ULN
• Total bilirubin ≤2× ULN
• Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease study equation)
• International normalized ratio (INR) below 1.1× ULN For subjects on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease.
• Platelet count ≥100×103/µL NOTE: PT, INR, and platelets can be performed locally at the Screening Visit, if deemed necessary by the investigator after consultation with the medical monitor, in cases where centrally read samples are deemed invalid.
• Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
Exclusion Criteria:

• Previous exposure to seladelpar (MBX-8025).
• A medical condition other than PBC that, in the investigator's opinion, would preclude full participation in the study (e.g., cancer) or confound its results (e.g., Paget's disease, any active infection).
• Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal AND total bilirubin above 1.0× ULN)
• Presence of clinically important hepatic decompensation, including the following:
• History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score ≥12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with their current dose adjustments of their anticoagulant medication, will be taken into account when calculating the MELD score. This will be done in consultation with the medical monitor.
• Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (ege.g., transjugular intrahepatic portosystemic shunt placement), ascites, and hepatic encephalopathy.
• Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
• Other chronic liver diseases:
• Current features of AIH as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology.
• PSC determined by the presence of diagnostic cholangiographic findings.
• History or clinical evidence of alcoholic liver disease.
• History or clinical evidence of alpha-1-antitrypsin deficiency.
• History of biopsy confirmed NASH.
• History or evidence of Gilbert's syndrome with elevated total bilirubin.
• History or evidence of hemochromatosis.
• Hepatitis B, defined as the presence of hepatitis B surface antigen.
• Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
• History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
• Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
• Clinically important alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to quantify alcohol intake reliably.
• History of malignancy diagnosed or treated, actively or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening.
• Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening
• Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening
• Treatment with anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening
• Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
• For females, pregnancy or breastfeeding
• Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the investigator
• Immunosuppressant therapies
• Other medications that effect liver or GI functions, such as absorption of medications or the roux-en-y gastric bypass procedure, may be prohibited and should be discussed with the medical monitor on a case-by-case basis.
• Active COVID-19 infection during Screening.
Drug: Seladelpar 10 mg, Drug: Placebo, Drug: Seladelpar 5 mg
Primary Biliary Cholangitis
Primary Biliary Cholangitis (PBC), PBC
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SHP620-302: A Phase 3, Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Compared to Valganciclovir for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients

Drug study - Maribavir in HSCT patients with CMV infections

Jo-Anne Young, MD
All
16 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT02927067
1703M11501
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Inclusion Criteria:

• Be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participants before completing any study-related procedures. During the COVID-19 public health emergency, informed consent from a potential or current trial participant may, if permitted by local laws and regulations, be obtained via electronic informed consent (eIC) capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site (FDA COVID-19 Guidance, 27 January 2021, Q11).
• Be greater than or equal to (>=) 16 years of age at the time of consent.
• Be a recipient of hematopoietic stem cell transplant.
• Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=1365 International Units per millilitre (IU/mL) to less than or equal to (<=) 273000 IU/mL in whole blood or >=455 IU/mL to <=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator. Participants with CMV DNA less than (<) 910 and >=455 IU/mL in plasma or <2730 and >=1365 IU/mL in whole blood will also need to meet at least 1 of the following criteria for high-risk CMV infection to be eligible:
• Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at 1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,
• Haploidentical donor
• Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
• Use of umbilical cord blood as stem cell source,
• Use of ex vivo T-cell-depleted grafts,
• Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of systemic corticosteroids (defined as the use of >=1 milligram per kilogram per day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).
• Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation, which in the investigator's opinion requires treatment.
• Per investigator's judgment, be eligible for treatment with valganciclovir.
• Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
• Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].
• Platelet count >=25,000/mm^3 [25*10^9/L].
• Hemoglobin >=8 grams per deciliter (g/dL).
• Estimated creatinine clearance >=30 milliliters per minute (mL/min).
• Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Urine pregnancy tests may be done per institutional requirements; however they are not sufficient for eligibility determination. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward the last dose of study treatment.
• Be able to swallow tablets.
• Have life expectancy of >=8 weeks.
• Weigh >=40 kilograms (kg).
• Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
Exclusion Criteria:

• Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
• Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
• Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a participants who had at least one previously documented episode of CMV infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA between the episodes during active surveillance, based on same local laboratory and same sample type). The Participants must also have been off any anti-CMV treatment between the current and prior infection. Otherwise, the current infection may be considered continuation of the prior infection.
• Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] co-infection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
• Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. Note: Participants who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use 3 days prior to first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.
• Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or letermovir) for the current CMV infection for longer than 72 hours.
• Have known hypersensitivity to the active substance or to an excipient of the study treatments.
• Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral medication.
• Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
• Be female and pregnant or nursing.
• Have previously completed, discontinued, or have been withdrawn from this study.
• Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
• Have received any unapproved agent or device within 30 days before initiation of study treatment.
• Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
• Have previously received maribavir.
• Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory.
• Have known (previously documented) positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
• Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
• Be undergoing treatment for acute or chronic hepatitis C
Drug: Maribavir, Drug: Valganciclovir, Other: Placebo
Cytomegalovirus (CMV)
Clinics and Surgery Center (CSC)
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A Phase II Multicenter, Randomized, Double-Blind, 12-Week Treatment, 3-Arm, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy, Safety and Tolerability of RO7017773 in Participants Aged 15 to 45 Years with Autism Spectrum Disorder (ASD)

Phase II Multicenter, Randomized, Double-Blind, 12-Week Treatment, 3-Arm, Parallel-Group, Placebo-Controlled Study

Suma Jacob
All
15 Years to 45 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04299464
STUDY00010423
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Inclusion Criteria
• Male and female participants with Autism Spectrum Disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Wechsler Abbreviated Scale of Intelligence (WASI-II) >/= 50 at screening or within the last 12 months prior to screening
• ASD or Autism diagnosis confirmed by Autism Diagnostic Observation Schedule (ADOS-2)
• Body mass index within the range of 18.5 to 40 kg/m2
• Female Participants: is eligible if she is not pregnant, not breastfeeding, and women of childbearing potential (WOCBP), who agree to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 28 days after the last dose of study drug
• Language, hearing, and vision compatible with the study measurements as judged by the Investigator
• Allowed existing treatment regimens should be stable for 8 weeks prior to screening. Investigator expects stability of these treatments and behavioral interventions for the duration of the study
• In the Investigator's opinion, able to participate and deemed appropriate for participation in the study, capable of following the study SoA and able to comply with the study restrictions
• In the Investigator's opinion, participation in the study or discontinuation of prohibited medication will not pose undue risks Exclusion Criteria Neurologic/Psychiatric Conditions:
• Non-verbal individuals
• Presence of chromosome 15q11.2 q13.1 duplication syndrome (Dup15q syndrome) genetically defined ASD per genetic results available prior to screening or known "syndromic" forms of ASD (e.g., fragile X syndrome, Prader Willi syndrome, Rett's syndrome, or tuberous sclerosis).
• Medical history of alcohol and/or substance abuse/dependence in the last 12 months or positive test for drugs of abuse at screening
• Initiation of a major change in psychosocial intervention within 6 weeks prior to screening. Minor changes in ongoing treatment are not considered major changes
• Clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
• Risk of suicidal behavior in the opinion of a certified clinician or as evidenced by a "yes" to questions 4 and/or 5 of Columbia-Suicide-Severity Rating Scale (C-SSRS) taken at screening and baseline with respect to the last 12 months, or any suicide attempt in the past 5 years
• Unstable epilepsy/seizure disorder within the past 6 months or changes in anticonvulsive therapy within the last 6 months Other Conditions:
• Medical history of malignancy if not considered cured or if occurred within the last 3 years with the exception of fully excised non-melanoma skin cancers or in-situ carcinoma of the cervix that has been successfully treated
• Concomitant disease, condition or treatment which would either interfere with the conduct of the study or pose an unacceptable risk to the participant in the opinion of the Investigator Prior/Concomitant Therapy
• Use of prohibited medications or herbal remedies within 6 weeks or 5 half-lives (t1/2) prior to randomization Prior/Concurrent Clinical Study Experience:
• Donation or loss of blood over 500 mL in adults and 250 mL in adolescents within 3 months prior to randomization
• Participation in an investigational drug study within 1 month or 5 times the t1/2 of the investigational molecule prior to randomization or participation in a study testing an investigational medical device within 1 month prior to randomization or if the device is still active Diagnostic Assessments
• Confirmed clinically significant abnormality in hematological, chemistry or coagulation laboratory parameters
• Positive test result at screening for hepatitis B surface antigen, hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA, may be considered eligible for entry into the study Other Exculsions:
• Uncorrected hypokalemia or hypomagnesaemia
Drug: Placebo, Drug: RO7017773
Autism Spectrum Disorder (ASD)
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VX20-121-102: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)

This is a Phase 3, randomized, double-blind, ELX/TEZ/IVA-controlled, parallel-group, multicenter study to evaluate the efficacy of VX-21/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in cystic fibrosis (CF) subjects who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Joanne Billings
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05033080
STUDY00013058
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Key
Inclusion Criteria:

• Heterozygous for F508del and a minimal function mutation (F/MF genotype)
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA Key
Exclusion Criteria:

• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Pregnant or breast-feeding females Other protocol defined Inclusion/Exclusion criteria may apply
Drug: VX-121/TEZ/D-IVA, Drug: ELX/TEZ/IVA, Drug: IVA, Drug: Placebo (matched to VX-121/TEZ/D-IVA), Drug: Placebo (matched to ELX/TEZ/IVA), Drug: Placebo (matched to IVA)
Cystic Fibrosis, Rare Diseases
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A double-blind, randomized, vehicle controlled, crossover study to evaluate the safety and efficacy of topical naloxone hydrochloride lotion, 0.5%, for the relief of pruritus in patients with the mycosis fungoides (MF) form of cutaneous t-cell lymphoma (CTCL)

The primary objective is to evaluate the safety and efficacy of topically applied naloxone lotion, 0.5%, for the treatment of pruritus in patients with the mycosis fungoides (MF) or Sézary syndrome (SS) Forms of Cutaneous Tcell Lymphoma (CTCL).

Kim Bohjanen, MD
All
21 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT02811783
STUDY00002462
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Inclusion Criteria:
All subjects must meet the following criteria for admission into the study:
• Signed informed consent has been obtained.
• Subject is at least 21 years of age.
• Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS) will be based on a combination of histological, clinical, and immunophenotypical criteria. The histological criteria will be based on skin biopsy from the most representative skin area. The diagnostic criteria used for each subject will be specified in the case report forms and the specific classification of MF or SS will be identified. The TNMB system will be used to classify the stage of disease (See Section 8.4 for details).
• Completion of the mSWAT assessment.
• A history of pruritus that meets following criteria: At Screening Day -7:
• present on a daily basis for greater than one month prior to Screening Day -7,
• NRS for Pruritus score ≥5 as rated by the subject at the Day -7 Visit. Note: If the score is <5 and subject is taking or has taken a medication which may be affecting pruritus (e.g. systemic antihistamine or topical steroid), and if Investigator and subject agree, subject may washout or continue washout of medication and return for Day -7 Visit procedures after washout. At Baseline Period 1 Day 0:
• NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4 of the 7 days preceding Baseline Period 1 Day 0.
• Pruritic treatment area of 5-95% of the subject's total treatable body surface area.
• Subject can be expected to reliably follow treatment instructions and visit schedule.
• Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout the study or females of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year). A negative urine pregnancy test must be confirmed at Baseline screening for all female subjects who are not post-menopausal > 1 year or surgically sterile.
• The subject agrees not to begin any new concomitant medications during their participation in the study, with the exception of medications necessary to treat infection, and to continue any concomitant medication throughout the study.
• Subject has no visual or motor impairments that will make it difficult to complete the Daily Diary or apply the study medication.
• Subject is able to speak, read, and write English and agrees to participate and comply with the study procedures.
• Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (see Appendix C, Body Mass Index Table) (subjects in PK subset only).
Exclusion Criteria:
Subjects meeting any of the following criteria will be excluded from study participation:
• Pregnant or lactating female.
• History of clinically significant heart failure.
• Myocardial infarction within the past six months.
• A history of ventricular arrhythmia requiring treatment.
• Any medical condition which would, in the Investigator's opinion, preclude the subject from successfully participating in the study.
• A known allergy to naloxone hydrochloride or any excipient in the formulation.
• Previous naloxone use for pruritus.
• Positive urine drug screen at Day 0 for opiates. Positive urine drug screen for anything other than opiates not explained, e.g., by concomitant medication, would also exclude the subject.
• Treatment with any of the following during the restricted time period prior to Day -7, and at any time during the study, is not allowed: Medication/Treatment Restriction: Systemic narcotic analgesics (e.g. morphine, codeine) 7 days, Topical antihistamines to any skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any therapies for the treatment of MF or SS) 30 days
Drug: Naloxone Hydrochloride Lotion, 0.5%, Drug: Placebo Lotion
Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Sézary Syndrome
Pruritus, Mycosis Fungoides, CTCL, naloxone, opiate antagonist, Sézary Syndrome, Clinics and Surgery Center (CSC)
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COG AALL1821 - A Phase 2 Study of Blinatumomab (NSC# 765986, IND# 147294) in Combination with Nivolumab (NSC # 748726, IND# 147294), a Checkpoint Inhibitor of PD-1, in B-ALL Patients Aged >/=1 to < 31 Years Old with First Relapse

The overall goal of this study is to determine if treating first relapse B-cell acute lymphoblastic leukemia (B-ALL) with a combination of blinatumomab and nivolumab is more effective than blinatumomab alone.

Peter Gordon
All
1 Year to 30 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04546399
STUDY00012652
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Inclusion Criteria:

• Patients must be >= 1 and < 31 years at time of enrollment
• Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories:
• Isolated bone marrow relapse
• Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
• Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes
• Patients with Down syndrome (DS) are eligible in the following categories:
• Isolated bone marrow relapse
• Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression
• Radiation therapy (RT): >= 3 months must have elapsed if prior RT. This includes any patient requiring urgent radiation to any sites of extramedullary disease prior to enrollment (e.g. retinal/optic nerve involvement)
• Hematopoietic stem cell transplant (HSCT): Patients must not have had a prior hematopoietic stem cell transplant
• A single intrathecal chemotherapy at the time of relapse will be allowed. If < 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted
• In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroid and/or hydroxyurea only) is permissible
• Group 1 and Down syndrome patients who received pre-enrollment therapy and have a white blood count (WBC) >= 30,000/ul at the time of enrollment must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required
• Group 1 and Down syndrome patients who received pre-enrollment therapy and have a WBC < 30,000/ul at the time of enrollment must be given a 24 hour "washout" before starting immunotherapy
• Note: There is no waiting period or "washout" for patients who relapse while receiving upfront therapy
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (within 7 calendar days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: 0.6 (male), 0.6 (female)
• 2 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram
• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
• 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:

• Patients with B-lymphoblastic lymphoma (B-LLy)
• Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
• Patients with Philadelphia chromosome positive (Ph+) B-ALL
• Patients with mixed phenotype acute leukemia (MPAL)
• Patients with known Charcot-Marie-Tooth disease
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype
• Patients with active, uncontrolled infection defined as:
• Positive bacterial blood culture within 48 hours of study enrollment
• Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection if cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline.
• Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed if blood cultures are negative for > 48 hours
• A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
• Active viral or protozoal infection requiring IV treatment
• Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible
• Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement
• Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
• Patients with an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Group 1 and DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible
• Note: Group 2 and 3 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if this is NOT the only site of relapsed disease
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab. Men receiving nivolumab and who are sexually active with WOCBP must continue contraception for 7 months after the last dose of nivolumab
• Lactating females are not eligible unless they agree not to breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose
Radiation: 3-Dimensional Conformal Radiation Therapy, Biological: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Etoposide, Drug: Hydrocortisone Sodium Succinate, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Biological: Nivolumab, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine Sulfate
Down Syndrome, Recurrent B Acute Lymphoblastic Leukemia
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A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of Sotatercept versus Placebo for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection Fraction (HFpEF) (CADENCE)

This Phase 2, double-blind, randomized, placebo-controlled, interventional study is designed to evaluate the efficacy, measured by change from baseline in PVR (primary endpoint) and 6MWD (key secondary endpoint) of sotatercept versus placebo in adults with Cpc-PH due to HFpEF. Safety: The safety and tolerability of sotatercept versus placebo in adults with Cpc-PH due to HFpEF will be assessed by the secondary endpoints.

Thenappan Thenappan
All
18 Years to 85 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04945460
STUDY00014234
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Inclusion Criteria:
Participants must meet the following criteria to be enrolled in this proof-of-concept study:
• Age 18 to 85 years
• Clinical diagnosis of HFpEF: • Left ventricular ejection fraction ≥ 50%, with no history of LVEF below 45%
• Demonstrated Cpc-PH by all of the following:
• Baseline RHC performed within 10 days prior to Visit 1 (during the Screening Period) documenting a minimum PVR of ≥ 320 dyn•sec/cm5 (4 wood units)
• Mean pulmonary arterial pressure (mPAP) of > 20 mmHg
• Pulmonary capillary wedge pressure (PCWP) > 15 mmHg but < 30 mmHg
• New York Heart Association FC of II or III
• Six-Minute Walk Distance ≥ 100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value
• Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for ≥ 30 days prior to Visit 1. Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within 30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1. Anticoagulation may be suspended for RHC if necessary.
• Women of childbearing potential must:
• Have a negative pregnancy test as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
• If sexually active, have used and agree to continue to use highly effective contraception without interruption for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study drug
• Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug See Appendix 2 for additional contraceptive information.
• Male participants must:
• Agree to use a condom, defined as a male latex condom or non latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy
• Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug
• Ability to adhere to the study visit schedule and understand and comply with all protocol requirements
• Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study
• Ability to understand and provide written informed consent for participation
Exclusion Criteria:
Participants will be excluded from the study if any of the following criteria are met:
• A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
• Significant parenchymal lung disease (e.g., chronic obstructive pulmonary disease with Global Initiative for Obstructive Lung Disease (GOLD) criteria III and IV, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
• Cardiovascular co-morbidities, which include any of the following:
• Any history of greater than mild mitral regurgitation or aortic regurgitation valvular disease or greater than mild aortic or mitral stenosis
• Acute coronary syndrome, coronary artery bypass graft or percutaneous coronary intervention within 180 days of Visit 1
• Uncontrolled heart rate (> 100 bpm) from atrial fibrillation or atrial flutter
• History of serious life-threatening or hemodynamically significant arrhythmia
• History of or anticipated heart transplant or ventricular assist device implantation
• History of or anticipated implantation of pacemaker or implantable cardioverter defibrillator
• Occurrence of myocardial infarction within 90 days of Visit 1
• History of known pericardial constriction, hypertrophic cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 110 mmHg during Screening after a period of rest
• Systemic hypotension as evidenced by sitting systolic blood pressure < 90 mmHg or sitting diastolic blood pressure < 50 mmHg during Screening
• Resting heart rate of < 45 bpm or > 115 bpm
• Cerebrovascular accident within 90 days of Visit 1
• Acutely decompensated HF within 45 days prior to Visit 1, as per investigator assessment
• Electrocardiogram (ECG) during Screening Period with Fridericia's corrected QT interval (QTcF) > 480 msec or > 500 msec if a ventricular conduction defect (right bundle branch block; left bundle branch block; or interventricular conduction delay) is present
• Personal or family history of long corrected QT syndrome or sudden cardiac death in first-degree relative
• Hospitalization for any indication within 30 days of Visit 1
• Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5 inhibitors, or soluble guanylate cyclase stimulators) within 30 days prior to Visit 1
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to Visit 1
• Received erythropoietin within 6 months prior to Visit 1
• Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A through C)
• Prior exposure to sotatercept or luspatercept
• Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
• Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Visit 1 or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
• Any of the following clinical laboratory values prior to Visit 1 as specified:
• Hemoglobin (Hgb) above the gender-specific upper limit of normal (ULN) per local laboratory test within 28 days of Visit 1or < 10 g/dL per local laboratory within 28 days of Visit 1
• Serum alanine aminotransferase or aspartate aminotransferase levels > 3× ULN or total bilirubin > 1.5× ULN within 28 days of Visit 1
• Estimated glomerular filtration rate < 30 ml/min/1.73 m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of Visit 1 or required renal replacement therapy within 90 days of Visit 1
• Glycated hemoglobin (HbA1c) > 10% within 28 days of Visit 1
• Platelet count < 75,000/mm3 within 28 days of Visit 1
• History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
• Major surgery within 60 days prior to Visit 1. Participants must have completely recovered from any previous surgery prior to Visit 1
• Prior heart-lung transplants or life expectancy of < 12 months
• Pregnancy or breastfeeding in females
• History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or ≤ 2 squamous cell carcinomas of the skin
• History of clinically significant (as determined by the investigator) endocrine, hematologic, hepatic, (auto)immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study
• Body mass index ≥ 45 kg/m2
Drug: Sotatercept, Drug: Placebo
Cpc-PH Due to HFpEF (Combined Post-capillary and Pre-capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction)
Pulmonary, hypertension, Cpc PH, HFpEF, sotatercept, Clinics and Surgery Center (CSC)
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A Partially-Blind, Randomized, Parallel-Group Dose Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFactTM (Aerosolized SF-RI 1) Administered by nCPAP versus nCPAP alone in the Treatment of Preterm Infants at Risk for Worsening Respiratory Distress Syndrome

A Partially-Blind, Randomized, Controlled, Parallel-Group Dose Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFactTM (SF-RI 1 surfactant for inhalation combined with a dedicated drug delivery system) in Preterm Infants at Risk of Worsening Respiratory Distress Syndrome. To determine an optimal dose of AeroFact™ administered to preterm infants on nCPAP or nIMV vs. nCPAP or nIMV alone in reducing the incidence of intubation/cannulation and bolus surfactant instillation in the first 7 days after birth. To evaluate pulmonary outcomes and respiratory resource utilization at 3, 6, 9, and 12 months PMA

Catherine Bendel
All
26 Weeks to 31 Weeks old
Phase 2
This study is NOT accepting healthy volunteers
NCT03969992
STUDY00007630
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Inclusion Criteria:

• Parental consent obtained prior to study procedures being performed (pre-natal consent is allowed)
• 26 0/7 to 30 6/7 weeks of gestational age
• Weight <2.0 Kg
• Respiratory Severity Score (RSS) 1.4-2.0
Exclusion Criteria:

• Apgar score less than or equal to 5 at five minutes after birth
• Need for chest compressions or administration of epinephrine or bicarbonate in the delivery room
• Premature rupture of membranes (PROM) > 14 days
• Need for intubation and/or mechanical ventilation prior to enrollment
• Active pneumothorax requiring chest tube
• Significant congenital anomaly, chromosomal abnormality
• Concomitant treatments with inhaled nitric oxide
Drug: AeroFact, Other: nCPAP
Respiratory Distress Syndrome in Premature Infant
Respiratory Distress Syndrome, BPD, surfactant, Preterm Infant
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MT2020-08 A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR0191 in subjects with Relapsed/Refractory Non-Hodgkin Lymphoma and r/r B-cell Acute Lymphoblastic Leukemia

To evaluate the safety and tolerability of PBCAR0191 in subjects with r/r B-ALL and r/r NHL and find an appropriate dose to optimize safety and efficacy. To evaluate the clinical benefit of PBCAR0191 in subjects with r/r B-ALL and r/r NHL. To evaluate the clinical activity of PBCAR0191 in subjects with r/r B-ALL and r/r NHL.

Joseph Maakaron
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03666000
STUDY00009953
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Key Inclusion Criteria* Criteria for B-ALL:
• Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow cytometry, or a validated minimal residual disease assay.
• Subjects with Philadelphia chromosome positive disease can be eligible if they are intolerant to tyrosine kinase inhibitor therapy or if they have r/r disease. Criteria for NHL:
• Subject has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding pathology report. Alternatively, if at least 1 tumor involved site is accessible at time of Screening, the subject's diagnosis is confirmed by pretreatment biopsy (excisional when possible) or by flow cytometry of fine needle aspirate. If a subject never had a CR, a sample from the most recent biopsy is acceptable. NHL subtypes included but are not limited to:
• Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
• FL including Grade 3 or transformed FL
• High-grade B-cell lymphoma
• Primary mediastinal lymphoma
• Subject has measurable or detectable (for example positron emission tomography-positive) disease according to the Lugano Classification.
• Subject must have received at least 2 prior chemotherapy-containing regimens, consistent with standard of care treatment guidance (e.g., NCCN), unless no second line therapy of known benefit exists for a given subject. Other than those specifically prohibited, other therapies are allowed until 7 days prior to initiation of LD. In that case, all Screening safety laboratories and disease assessments must be performed after the last dose of prior therapy. For Richter's transformation, only 1 prior line of therapy is required for the DLBCL component.
• Subject has received no more than 7 systemic lines of anti-cancer therapy for the disease under study.
• Subjects previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
• Expansion cohort only: Subjects must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse. Criteria for both B-ALL and NHL:
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
• Seronegative for human immunodeficiency virus antibody (i.e., intact immune function).
• Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
• Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (calculated using the CKD-EPI equation [Levey et al, 2009]). If there is a concern that eGFR calculation is not an accurate reflection of renal function, a 24-hour urine collection for creatinine clearance may be used at the investigator's discretion.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal (ULN), unless there is suspected disease in the liver.
• Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.
• Platelet count ≥50,000/μL and absolute neutrophil count of ≥1000/ μL. Platelet transfusions within 14 days of screening are not allowed except for subjects in B-ALL disease cohort with extensive bone marrow disease burden, in which case adequate bone marrow recovery after prior treatment is required to be documented.
• C-reactive protein (CRP) <2x ULN; subjects with CRP elevation within 2x ULN, ruling out infectious cause will be required.
• Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition scan performed within 1 month before starting lymphodepleting chemotherapy. ECHO results performed within 6 months before Screening and at least 28 days after the last cancer treatment may be acceptable if the subject has not received any treatment with cardiotoxicity risks.
• No clinically significant evidence of pericardial effusion or pleural effusion causing clinical symptoms and needing immediate intervention, based on the investigator's opinion. Any known effusion must be stable without need for drainage within 2 weeks of enrollment.
• No clinically significant renal/pulmonary comorbidities.
• Baseline oxygen saturation >92% on room air. Key Exclusion Criteria* Criteria for B-ALL:
• Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
• No active central nervous system (CNS) disease. Subjects with a history of CNS involvement must have a documented CR on at least 2 imaging studies at least 3 months apart (with no masses in parenchyma and no ocular involvement) and a negative cerebrospinal fluid cytology on at least 2 evaluations (one evaluation may be during the Screening Period and the other must be at least 3 months prior). Criteria for NHL:
• No prior or active CNS disease.
• Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
• Active hemolytic anemia. Criteria for B-ALL and NHL:
• Subject has had a malignancy, besides the malignancies of inclusion (B-ALL or NHL), that in the investigator's opinion, has a high risk of relapse in the next 2 years. In the case of Richter's transformation, subjects may be enrolled with ongoing chronic lymphocytic leukemia/small lymphocytic lymphoma.
• Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection that has not resolved and does require therapeutic anti-microbial medications at least 7 days prior to LD. Subjects with elevated CRP must undergo infectious disease workup and the recommendations discussed with medical monitor to be considered on an individual basis. The CRP must be trending toward the normal range for the laboratory with the exception when it's deemed related to the underlying malignancy.
• Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
• Active hepatitis B or hepatitis C confirmed by PCR. Subject positive for inactive hepatitis B is allowed to enroll if on prophylactic treatment.
• Subject is seropositive for hepatitis B antigen with confirmation. If confirmatory tests are negative, the subject can be enrolled.
• Subject is seropositive for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, the subject must be tested for the presence of RNA by reverse transcription PCR and be hepatitis C virus-RNA negative.
• Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the subject ineligible, including but not limited to:
• Active ventricular or atrial dysrhythmia ≥ Grade 2, bradycardia ≥ Grade 2.
• Myocardial infarction within 6 months before Screening.
• Pulmonary embolism, deep vein thrombosis, or any other significant coagulopathy including disseminated intravascular coagulation.
• History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening. In case of hypertensive crisis caused by omission of well-established treatment regimen, transient and promptly stabilized, enrollment must be discussed and agreed upon with sponsor and medical monitor.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Presence of a CNS disorder that, in the opinion of the investigator, renders the subject ineligible for treatment.
• Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject's safety.
• History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
• Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding subjects needing steroids for physiologic replacement).
• Subject has received stem cell transplant within 90 days before Screening.
• Subject has active GvHD symptoms.
• Subject has received systemic biologic agent for treatment of disease under study within 28 days of LD or other systemic anti-cancer therapy within 10 days of LD Note: this criterion does not apply if the subject has clear evidence of disease progression after such an agent has been administered and all AEs have resolved to a Grade 2 or less in severity. This should be discussed with the medical monitor for confirmation.
• Participation in noninterventional registries or epidemiological studies is not excluded.
• Radiotherapy within 4 weeks before Screening should be discussed with monitor and determined on a case-by-case basis.
• Presence of pleural/peritoneal/pericardial catheter, as well as biliary and ureteral stents (does not apply to intravenous lines).
• Subject has received live vaccine within 4 weeks before Screening. Non-live virus vaccines are not excluded.
• Subject has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD.
• Additional criteria apply
Genetic: PBCAR0191, Drug: Fludarabine, Drug: Cyclophosphamide
Non-Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia
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MT2020-34: A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants (from 1 month to < 18 years of age) with Thrombotic Microangiopathy (TMA) after Hematopoietic Stem Cell Transplantation (HSCT)

To assess the efficacy of ravulizumab plus BSC in the treatment of pediatric participants with HSCT-TMA.

Jessica Knight-Perry
Phase III
This study is NOT accepting healthy volunteers
NCT04557735
STUDY00011217
Thrombotic Microangiopathy
Hematopoietic Stem Cell Transplant, Ravulizumab, Thrombotic Microangiopathy (TMA), Ultomiris
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MT2020-21: A PHASE 1,OPEN-LABEL,DOSE ESCALATING STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND CLINICAL ACTIVITY OF THE COMBINATION OF CLBR001, AN ENGINEERED AUTOLOGOUS T-CELL PRODUCT, AND SWI019,AN ANTIBODY-BASED BIOLOGIC, IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL MALIGNANCIES

This study is designed to assess the safety and tolerability of the combination of CLBR001 and SWI019 in patients with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation.

Joseph Maakaron
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04450069
STUDY00011917
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Inclusion Criteria:

• Patients with relapsed / refractory previously treated B cell malignancies (according to the World Health Organization classification; 2017)
• Chemotherapy-refractory disease
• Patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-containing chemotherapy, anti-CD20 (cluster of differentiation antigen 20) therapies and/or Brutton's tyrosine kinase (BTK) inhibitors
• Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have confirmed CD19+ disease
• Patients must be ineligible for allogeneic stem cell transplant (SCT)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered
• Willing to undergo pre- and post-treatment core needle biopsy
• Adequate hematological, renal, pulmonary, cardiac, and liver function
• Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1
• Women of childbearing potential, a negative pregnancy test and must agree to practice effective birth control
• Men sexually active with female partners of child bearing potential must agree to practice effective contraception
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures
Exclusion Criteria:

• Patients diagnosed with disease histologies including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance (MGUS), T-cell histiocyte large B cell lymphoma
• Pregnant or lactating women
• Active bacterial, viral, and fungal infections
• History of allogeneic stem cell transplantation
• Treatment with any prior lentiviral or retroviral based CAR-T
• Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or need for live vaccine on study
• Patients with known active central nervous system (CNS) disease. Patients with prior CNS disease that has been effectively treated may be eligible
• History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial infarction, unstable angina or other significant cardiac disease within 6 months of screening
• Involvement of cardiac tissue by lymphoma
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)
• HIV-1 and HIV-2 antibody positive patients
Combination Product: CLBR001 and SWI019
Relapsed/Refractory B-cell Lymphomas, Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Chronic Lymphocytic Leukemia (CLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma, Small Lymphocytic Lymphoma (SLL), Primary Mediastinal Large B Cell Lymphoma, Transformed Follicular Lymphoma
CAR-T Cell Therapy, Switchable CAR-T Cell, Autologous Cell Therapy, CD19 Positive Disease, CD19 CAR-T Cell, Blood Cancer, Hematological malignancy, Neoplasms, Clinics and Surgery Center (CSC)
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Phase 1/2 First-in-Human (FIH) Study of Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2) Inhibitor Monoclonal Antibody (mAb) JTX-8064, as Monotherapy and in Combination with a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, in Adult Subjects with Advanced Refractory Solid Tumor Malignancies

The purpose of this study is to find out: •What dose of JTX-8064 is safe and tolerable either when given by itself or in combination with JTX-4014 or pembrolizumab. •What effects, both good and bad, JTX-8064 may have when given alone or in combination with JTX-4014 or pembrolizumab. •How much JTX-8064 gets into the bloodstream and how long it takes for the body to get rid of it. •Whether the body generates an immune response against JTX-8064 that could possibly have a negative effect on its ability to work.

Deanna Teoh
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04669899
STUDY00013057
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• Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures;
• Histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy.
• Stages 1 and 2: Subject must have received, have been intolerant to, have been ineligible for, or have declined all treatment known to confer clinical benefit with the exception of subjects enrolled in combination cohorts with a PD-1i, where a PD-1i is approved by the local regulatory agencies
• Stage 3: This stage may enroll subjects with the following cancers: • 3L/4L PD-(L)1-naïve, platinum-resistant ovarian cancer
• Stage 4: This stage may enroll subjects with the following cancers:
• 2L/3L ccRCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy
• 2L-4L TNBC. Subjects must have progressed on or after treatment with a prior anti-PD-(L)1 therapy
• 1L, PD-(L)1-naïve, PD-L1+; combined positive score (CPS) ≥ 1% HNSCC
• 3L/4L, PD-(L)1-naïve, platinum-resistant ovarian cancer
• 2L/3L NSCLC; Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy. Subjects with EGFR mutations and ALK rearrangements will be excluded. Subjects with other targetable genomic aberrations for which FDA approved therapies exist must have received appropriate FDA-approved targeted therapy
• 2L/3L cSCC; Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy
• 2L-4L PD-(L)1-naïve UPS and LPS
• 2L/3L HNSCC. Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy.
• Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator;
• ≥ 18 years of age;
• Eastern Cooperative Oncology Group performance status 0 or 1;
• Predicted life expectancy of ≥ 3 months;
• Have specified laboratory values (obtained ≤ 28 days prior to first dose) in accordance with the study protocol;
• For women of childbearing potential (WOCBP): negative serum pregnancy test during the Screening period and a negative urine pregnancy test up to 24 hours in advance of C1D1
• WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration.
Exclusion Criteria:

• Concurrent anticancer treatment, either FDA approved or investigational, for the cancer being evaluated in this study or for prior malignancies. A past history of other malignancies is allowed as long as the subject is not receiving treatment other than hormonal therapy and, in the judgment of the Investigator, is unlikely to have a recurrence. Of note, concurrent malignancies that do not require treatment and are clinically stable are allowed
• Prior infusion of JTX-8064, LILRB2, or ILT4-directed therapy;
• The therapies listed below within the specified timeframe:
• Immunotherapy or biologic therapy < 28 days prior to planned C1D1 or 5 half-lives, whichever is shorter
• Chemotherapy < 21 days prior to planned C1D1, or < 42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter
• Targeted small molecule therapy < 14 days or 5 half-lives, whichever is shorter, prior to planned C1D1
• Radiation therapy < 21 days prior to planned C1D1. Exception: Limited (e.g., pain palliation) radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities, any AE due to prior radiation therapy has recovered to < Grade 2, and the radiation is not administered to a target lesion
• Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation (brain metastases that are stable and asymptomatic after prior treatment will be allowed);
• Women who are pregnant or breastfeeding or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study
• Live vaccines ≤ 30 days of C1D1
Drug: JTX-8064, Drug: pimivalimab
Cancer
JTX-8064, LILRB2, ILT-4, PD-1, JTX-4014, Immunotherapy, Immuno-oncology, Solid tumor Malignancies, Dose escalation, INNATE, Monotherapy, Combination Therapy, Antineoplastic Agents, Immunological, Clinics and Surgery Center (CSC), Phase I Clinic
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