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Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M;(ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant
The study hypothesis is that the administration of Viralym-M to patients with virus-associated HC will demonstrate superiority for the time to resolution of HC (as measured by resolution of macroscopic hematuria) compared to patients treated with placebo. The primary hypothesis will be tested in patients with BKV viruria to demonstrate superiority over placebo in this population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted in all patients with any viral-associated HC (BKV, JCV, AdV, EBV, CMV, and/or HHV-6) in order to evaluate efficacy in this broader population (ITT Population). Further detail is provided in the statistical section below and will be described in the Statistical Analysis Plan (SAP).
Jo-Anne Young, MD
All
Not specified
Phase 3
STUDY00011838
STUDY00011838
Key Inclusion Criteria
Participants must meet all of the following criteria in order to be eligible to participate in the study:
Male or female ≥1 year of age.
Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm³ at the time of randomization.
Diagnosed with HC based on the following criteria (all 3 criteria must be met):
Clinical signs and/or symptoms of cystitis.
Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available.
Key Exclusion Criteria
Participants who meet any of the following criteria will be excluded from participation in the study:
Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
Evidence of active Grade >2 acute graft versus host disease (GVHD).
Uncontrolled or progressive bacterial or fungal infections.
Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
Pregnant or lactating or planning to become pregnant.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Posoleucel (ALVR105), Placebo, Posoleucel (ALVR105), Placebo
Cancer, Infectious Diseases
Clinics and Surgery Center (CSC)
Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) and Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40% (FINEARTS-HF) (FINEARTS-HF)
This study is a randomized, double-blind, parallel-group, placebo-controlled, multicenter, event-driven Phase 3 study with independently adjudicated clinical outcome assessments.
Tamas Alexy
All
40 Years to old
Phase III
STUDY00010807
STUDY00010807
Inclusion Criteria:
Participant (male or female) must be aged 40 years and older.
Diagnosis of heart failure with New York Heart Association(NYHA) class II-IV, ambulatory or hospitalized primarily for heart failure.
On diuretic treatment for at least 30 days prior to randomization.
Documented left ventricular ejection fraction (LVEF) of ≥40% measured by any modality within the last 12 months.
Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: left atrial diameter (LAD) ≥3.8cm, left atrial area (LAA) ≥20cm2, left atrial volume index (LAVI) >30 mL/m2, left ventricular mass index (LVMI) ≥115 g/m2 (♂)/ 95 g/m2 (♀), septal thickness or posterior wall thickness ≥1.1 cm
n-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL (BNP ≥100 pg/mL) in sinus rhythm and patient does not have an ongoing diagnosis of paroxysmal atrial fibrillation or NT-proBNP ≥900 pg/mL (BNP ≥300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrillation) for participants obtained at the following time:
Within 90 days prior to randomization if patient had been hospitalized for heart failure (HF) requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization OR
Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days.
Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and baseline and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for those participating in clinical trials.
Exclusion Criteria:
Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m² at either screening or randomization visit.
Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit.
Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization
Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization
Coronary artery bypass graft surgery in the 90 days prior to randomization
Percutaneous coronary intervention in the 30 days prior to randomization
Stroke or transient ischemic cerebral attack within 90 days prior to randomization
Probable alternative cause of participants' HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnea such as significant pulmonary disease, anemia or obesity. Specifically, patients with the below are excluded: Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy, History of primary pulmonary arterial hypertension, Hemoglobin <10 g/dl, Valvular heart disease considered by the investigator to be clinically significant, Body Mass Index (BMI) >50 kg/m2 at screening
Systolic blood pressure(SBP) ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at randomization.
Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) or moderate or potent CYP3A4 inducers, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period. Finerenone (BAY94-8862), Placebo, Finerenone (BAY94-8862), Placebo
Heart Failure
Clinics and Surgery Center (CSC)
A prospective, randomized, active (warfarin) controlled, parallel-arm clinical trial to determine if patients with an On-X aortic valve can be maintained safely and effectively on the factor Xa inhibitor Apixaban.
A prospective, randomized, active (warfarin) controlled, parallel-arm clinical trial to determine if patients with an On-X aortic valve can be maintained safely and effectively on the factor Xa inhibitor apixaban
Andrew Shaffer
All
18 Years to old
Phase 3
STUDY00010697
STUDY00010697
Inclusion Criteria:
Male or female at least 18 years of age at the time of giving informed consent.
Participants currently receiving warfarin anticoagulation and who are able to receive warfarin with a target INR 2.0 to 3.0.
Participants are able to take low-dose aspirin at a dose of 75 -100 mg daily or have a documented contraindication to aspirin use.
Implantation of an On-X mechanical valve in the aortic position at least 3 months (90 days) ago.
Female participants of childbearing potential, including those who are less than 2 years post-menopausal, must agree to, and comply with using a highly effective method of birth control (eg, barrier contraceptives [condom or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices or sexual abstinence) while partaking in this study. In addition, all women of childbearing potential must agree to continue to use birth control throughout the study until last study visit.
Informed of the full nature and purpose of the study, including possible risks and side effects, given ample time and opportunity to read and understand this information, and sign and date the written informed consent before inclusion in the study.
Exclusion Criteria:
Mechanical valve in any position other than aortic valve.
Any cardiac surgery in the three months (90 days) prior to enrollment.
Need to be on aspirin >100 mg daily or a P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel, or ticlopidine).
Known hypersensitivity or other contraindication to apixaban.
On dialysis or a creatinine clearance < 25 mL/min.
Ischemic stroke or intracranial hemorrhage within 3 months.
Active pathological bleeding at the time of screening for enrollment.
Active endocarditis at the time of screening for enrollment.
Pregnant, plan to become pregnant, or are breast feeding.
On concomitant combined strong P-gp and CYP3A4 inducers or inhibitors.
History of non-compliance with recommended monthly INR testing. Apixaban 5 MG, Apixaban 2.5 MG, Warfarin, On-X Aortic Mechanical Valve, Apixaban 5 MG, Apixaban 2.5 MG, Warfarin, On-X Aortic Mechanical Valve
Aortic Valve Disease, Aortic Valve Stenosis, Aortic Valve Failure
Clinics and Surgery Center (CSC)
COG ALTE2031 - StepByStep: A Randomized Trial of a Mobile Health and Social Media Physical Activity Intervention among Adolescent and Young Adult Childhood Cancer Survivors
The study objectives are to compare the effect of 2 different physical activity programs on physical activity levels in adolescents and young adults who received and completed treatment for cancer and to measure lab tests associated with heart health and information collected from surveys to learn how changes in physical activity levels affect health and quality of life in participants.
Lucie Turcotte
All
15 Years to 20 Years old
Phase 3
STUDY00013015
STUDY00013015
Inclusion Criteria:
First diagnosis of malignant neoplasm (International Classification of Diseases for Oncology [ICD-O] behavior code of "3") in first and continuous remission at the time of enrollment
Curative cancer treatment must have included chemotherapy (including cellular therapy) and/or radiation (including radioactive iodine)
Note: Childrens Oncology Group (COG) therapeutic trial participation is not required
All cancer treatment must have been completed within 3-36 calendar months prior to enrollment
Patients must have a life expectancy of > 1 year
Self-report of < 420 minutes of moderate-to-vigorous physical activity per week as assessed via the study-specific Physical Activity Worksheet
Note: See COG Study Web Page for the Godin-Shephard Leisure Time Physical Activity Questionnaire or link to online calculator
Ambulatory and no known medical contraindications to increasing physical activity
Note: Patients with amputation, rotationplasty, or other prothesis are not automatically excluded as long as they are ambulatory and have no known medical contraindications to increasing physical activity and all other eligibility criteria are satisfied
No known significant physical or cognitive impairment that would prevent use of the electronic devices used for the protocol intervention (e.g. Fitbit, smartphone, tablet, or computer)
Able to read and write English
Note: For patients < 18 years, consenting parent/legal guardian does not have to be able to read and write English
All patients and/or their parents or legal guardians must sign a written informed consent
Note: Informed consent may be obtained electronically/online if allowed by local site policy and Institutional Review Board (IRB)/Research Ethics Board (REB) of record
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Post-menarchal female patients who are pregnant or planning to become pregnant in the next year are excluded
Note: Pregnancy status can be established by clinical history with patient. Post-menarchal female patients are eligible as long as they agree to use an effective contraceptive method (including abstinence) during study participation
Patients with previous hematopoietic stem cell transplant (HSCT) are excluded
Note: Patients with previous autologous HSCT, chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate as long as all other eligibility criteria are satisfied Educational Intervention, FitBit, Goal Setting, Health Promotion and Education, Media Intervention, Telephone-Based Intervention, Educational Intervention, FitBit, Goal Setting, Health Promotion and Education, Media Intervention, Telephone-Based Intervention
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Site for ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications
We are continuing to study the SARS-CoV-2 coronavirus and the evolving new variants. We are looking at drugs that have Food and Drug Administration (FDA) approval for other uses. The goal is to determine if these drugs can make participants who get the coronavirus feel better faster and reduce death and hospitalizations.
Carolyn Bramante
All
30 Years to old
Phase 3
STUDY00013589
STUDY00013589
Inclusion Criteria:
Completed Informed Consent
Age ≥ 30 years old
Confirmed SARS-CoV-2 infection by any authorized or approved polymerase chain reaction (PCR) or antigen test collected within 10 days of screening
Two or more current symptoms of acute infection for ≤7 days. Symptoms include the following: fatigue, dyspnea, fever, cough, nausea, vomiting, diarrhea, body aches, chills, headache, sore throat, nasal symptoms, new loss of sense of taste or smell
Exclusion Criteria:
Prior diagnosis of COVID-19 infection (> 10 days from screening)
Current or recent (within 10 days of screening) hospitalization
Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo
Known contraindication(s) to study drug including prohibited concomitant medications Ivermectin, Fluvoxamine, Fluticasone, Placebo, Montelukast, Ivermectin, Fluvoxamine, Fluticasone, Placebo, Montelukast
Covid19
montelukast, SARS-CoV-2, COVID-19, ivermectin, Placebo, Duke University Health System, Outcomes, Duke Clinical Research Institute, fluticasone, fluvoxamine, ACTIV 6, ACTIV
The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT) (SURPASS-CVOT)
Study I8F-MC-GPGN (GPGN), also known as SURPASS-CVOT, is a Phase 3, event-driven, multicenter, international, randomized, double-blind, active comparator, parallel-group study. This study will assess the effect of QW tirzepatide (up to 15 mg) versus dulaglutide (1.5 mg) on CV outcomes when added to the standard of care in patients with T2DM with established cardiovascular disease and elevated risk for MACE.
Les Forgosh
Male or Female
18 Years and over
Phase III
STUDY00009070
STUDY00009070
Inclusion Criteria:
Have a diagnosis of type 2 diabetes
Have confirmed atherosclerotic cardiovascular disease
HbA1c ≥7.0% to ≤10.5%
Body mass index (BMI) ≥25 kilograms per meter squared (kg/m²)
Exclusion Criteria:
Have had a major cardiovascular event within the last 60 days
Have type 1 diabetes mellitus
Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the last 6 months
Are currently planning treatment for diabetic retinopathy and/or macular edema
Currently planning a coronary, carotid, or peripheral artery revascularization
Have a history of pancreatitis
Have a history of ketoacidosis or hyperosmolar state/coma
Have a known clinically significant gastric emptying abnormality, have undergone or currently planning any gastric outlet obstruction, or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery
Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years
Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement Tirzepatide, Dulaglutide, Tirzepatide, Dulaglutide
Diabetes & Endocrine, Heart & Vascular
Heart Disease, Type 2 Diabetes
A Randomized, Double-blind, Placebo-controlled, Multicenter Trial, Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Participants With Established Cardiovascular Disease (VICTORION-2 PREVENT) (VICTORION-2P)
CKJX839B12302 is a pivotal, randomized, double-blind, placebo controlled, multicenter Phase III trial, designed at assessing the benefits of inclisiran sodium 300 mg s.c., administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in addition to well-tolerated high-intensity statin therapy, on major adverse cardiovascular events (3P-MACE defined as first occurrence of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal ischemic stroke), in a secondary prevention cohort of atherosclerotic cardiovascular disease (ASCVD) participants with a LDL-C ≥1.8 mmol/L (70 mg/dL).
Daniel Duprez
All
40 Years to old
Phase III
STUDY00015316
STUDY00015316
Inclusion Criteria:
Fasting LDL-C ≥ 70 mg/dL at randomization visit
Stable (greater than or equal to 4 weeks) and well-tolerated lipid-lowering regimen (including e.g. with or without Ezetimibe) that must include a high-intensity statin therapy with either atorvastatin greater than or equal to 40 mg QD or rosuvastatin greater than or equal to 20 mg QD
Established CV disease defined as ANY of the following three conditions
Spontaneous Myocardial infarction ≥ 4 weeks from screening visit
History of ischemic stroke occurred ≥ 4 weeks prior to the Screening visit
Symptomatic peripheral arterial disease (PAD) evidenced by either intermittent claudication with ankle brachial index (ABI) < 0.85, prior peripheral arterial revascularization procedure, or, amputation due to atherosclerotic disease.
Exclusion Criteria:
Acute coronary syndrome, stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 4 weeks before screening visit
Treatment with PCSK9 inhibitors (e.g. evolocumab, alirocumab) within 90 days or planned use post first study visit
Planned or expected cardiac, cerebrovascular or peripheral artery surgery or re-vascularization within the 6 months after the first study visit
Heart failure NYHA class III or IV
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver
Previous exposure to inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug within 2 years
Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 5 years
History of malignancy that required surgery radiation therapy and/or systemic therapy during the 3 years prior to the first study visit
Pregnant or nursing (lactating) women
Other protocol-defined inclusion/exclusion criteria may apply. Inclisiran sodium 300 mg, Placebo, Inclisiran sodium 300 mg, Placebo
Atherosclerotic Cardiovascular Disease
Clinics and Surgery Center (CSC)
MT2021-33: Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation
To compare the percent of participants who have clearance of AdV viremia at Day 29 in participants receiving posoleucel and standard of care to that in participants receiving placebo and standard of care.
Paul Orchard
All
1 Year to old
Phase 3
STUDY00014640
STUDY00014640
Inclusion Criteria:
Male or female 1 year of age or older
Undergone allogeneic cell transplantation ≥21 days prior to dosing
Meet one of the below criteria:
AdV viremia DNA ≥10,000 copies/mL, OR
AdV viremia DNA results of ≥1,000 copies/mL, AND
has absolute lymphocyte count <180/mm3, OR
has received T cell depletion OR
had a cord blood transplant.
Exclusion Criteria:
Grade >2 acute GVHD
Ongoing therapy with high-dose systemic corticosteroids
Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
Pregnant or lactating female unwilling to discontinue nursing prior to randomization
History of severe prior reactions to blood product transfusions.
NOTE: Other protocol-defined inclusion/exclusion criterion may apply. Posoleucel, Placebo, Posoleucel, Placebo
Adenovirus Infection
Clinics and Surgery Center (CSC)
A Randomized, Parallel-Arm, Active Control, Multicenter Study Assessing the Safety and Efficacy of DEXTENZA for the Treatment of Ocular Pain and Inflammation Following Surgery for Pediatric Cataract
This randomized trial will compare the insertion of a DEXTENZA plug versus the standard prednisolone acetate suspension in the form of an eye drop to treat ocular pain and inflammation following cataract surgery. Its primary objective is to assess the safety of DEXTENZA compared to the control (prednisolone acetate) in children under the age of 6 years who are undergoing cataract surgery.
Raymond Areaux
All
0 Years to 3 Years old
Phase III
STUDY00010045
STUDY00010045
Inclusion Criteria:
Pediatric cataract diagnosis
Subject is >0 - 3 years of age
Exclusion Criteria:
Any intraocular inflammation in the study eye
Ocular hypertension or glaucoma
Evidence of acute external ocular infections Dextenza, Prednisolone, Dextenza, Prednisolone
Cataract
Dextenza, dexamethasone ophthalmic insert
Randomized Clinical Evaluation of the AccuCinch? Ventricular Restoration System in Patients who Present with Symptomatic Heart Failure with Reduced Ejection Fraction (HFrEF)
The objective of this study is to evaluate the safety and efficacy of the AccuCinch Ventricular Restoration System in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).
Greg Helmer
All
18 Years to old
N/A
STUDY00013236
STUDY00013236
Inclusion Criteria:
Age 18-years or older
Ejection Fraction: ≥20% and ≤40% measured by transthoracic echocardiography (TTE) and assessed by an echocardiography (echo) core lab
LV end-diastolic diameter ≥55 mm measured by TTE and assessed by an echo core lab
Symptom Status:
NYHA III,
NYHA ambulatory IV, or
NYHA II with a heart failure hospitalization within the prior 12 months (of signing the consent)
Able to complete six-minute walk test with distance between 100 m and 450 m.
Diagnosis and treatment for heart failure should be established at least 90 days before the date of consent. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current guidelines as standard-of-care for Heart Failure therapy, with any intolerance documented.
"Stable" is defined as no more than a 100% increase or a 50% decrease of total daily doses. Medication changes within this range do not require any additional waiting before the screening assessments
When a total daily dose increase or decrease exceeds that which is considered stable, the screening TTE and CT will be postponed 30 days after the medication change
When additional titration is required to optimize a subject's medication that exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the optimal dose remains outside of the stable parameters)
When a dose-for-dose equivalent change in the class of medication change is made, no additional waiting is required before the screening assessments
When a change in class medication change exceeds what is considered stable, OR a new class of medication is added, the screening TTE and CT will be postponed 30 days after the medication change
If an SGLT2 inhibitor is added to a subject's medications, the screening TTE and CT will be postponed at least 30 days after the addition
If an SGLT2 inhibitor dose changes per the stable definition above, no additional waiting is required before the screening assessments
If an SGLT2 inhibitor dose change exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the dose remains outside of the stable parameters)
When applicable, for guideline-directed device-based therapies: a CRT device must be placed > 90 days before the screening TTE and CT, and an ICD must be placed > 30 days before the screening TTE and CT
Able and willing to complete all qualifying diagnostic and functional tests, willing to accept blood product transfusion if required and agrees to comply with study follow-up schedule
Exclusion Criteria:
Cardiovascular
Myocardial infarction or any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 90 days prior to consent
Untreated clinically significant coronary artery disease (CAD) requiring revascularization
Fluoroscopic or echocardiographic evidence of severe aortic arch calcification, mobile aortic atheroma, intracardiac mass, thrombus or vegetation
Suboptimal ventricular anatomy or wall thickness as determined from screening echocardiography and/or CT scan
Heart failure on the basis other than ischemic or non-ischemic dilated cardiomyopathy (e.g., hypertrophic cardiomyopathy, amyloid cardiomyopathy, restrictive cardiomyopathy, uncorrected congenital heart disease, constrictive pericarditis)
Hemodynamic instability within 30 days prior to the implant defined as subject requiring inotropic support or mechanical hemodynamic support
Any planned cardiac surgery or interventions within the next 180 days post-randomization (including therapeutic right heart procedures)
Active bacterial endocarditis
Severe RV dysfunction assessed by right heart catheterization (RHC) and/or TTE
Fixed pulmonary hypertension with PA systolic pressure >70 mmHg not responsive to vasodilator therapy
History of any stroke within the prior 90 days of consent or documented Modified Rankin Scale ≥ 2 disability from any prior stroke
Valvular
Mitral regurgitation grade 3+ (moderate-severe) or 4+ (severe)
Untreated degenerative (primary) mitral valve disease (mild prolapse with no need for intervention is allowable)
Prior mitral or aortic valve replacement
Tricuspid regurgitation grade 4+ (severe)
Moderate or severe aortic valve stenosis (AVA less than 1.5 cm2 or peak velocity AV Vmax >300 cm/sec)
Aortic regurgitation grade 2+ (moderate), 3+ (moderate-severe), or 4+ (severe)
Procedural
Anatomical pathology or constraints preventing appropriate access/implant of the AccuCinch Ventricular Restoration System (e.g., femoral arteries will not support a 20F Introducer sheath)
Renal insufficiency (i.e., eGFR of <25 ml/min/1.73 m2)
Subjects in whom anticoagulation during the procedure is contraindicated
Subjects in whom 90 days of antiplatelet therapy is contraindicated
Known allergy to nitinol, polyester, or polyethylene
Any prior true anaphylactic reaction to contrast agents; defined as known anaphylactoid or other non-anaphylactic allergic reactions to contrast agents that cannot be adequately pre-medicated prior to the index procedure
General
Life expectancy <1 year due to non-cardiac conditions
Currently participating in another interventional investigational study
Subjects on high dose steroids or immunosuppressant therapy
Female subjects who are pregnant, of child-bearing potential without a documented birth control method, or who are lactating AccuCinch Ventricular Restoration System, Guideline-Directed Medical Therapy, AccuCinch Ventricular Restoration System, Guideline-Directed Medical Therapy
Heart Failure With Reduced Ejection Fraction (HFrEF), Dilated Cardiomyopathy
Clinics and Surgery Center (CSC)
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome - RECONNECT (RECONNECT)
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of CBD administered as ZYN002, a transdermal gel, for the treatment of children and adolescent patients with FXS. Qualified male and female patients with FXS will enter a two-week single-blind placebo lead-in period. Following the placebo lead-in, patients meeting randomization criteria will receive double-blind treatment for 16 weeks. The study will be comprised of a Screening visit and a combination of seven onsite (face-to-face) and virtual study visits. Approximately 204 male and female patients, ages 3 to < 18 years, will be randomized 1:1 to either trial drug or placebo. Randomization will be stratified by gender (male, female), methylation status (complete, partial), and by weight (≤50 kg, >50 kg).
Amy Esler
All
3 Years to 23 Years old
Phase 3
STUDY00014264
STUDY00014264
Inclusion Criteria:
Male or female children and adolescents aged 3 to < 23 years, at the time of Screening.
Patient resides with caregiver who will continue to provide consistent care throughout the study.
Judged by the Investigator to be in generally good health at Screening based upon the results of medical history, physical exam, 12-lead ECG and clinical laboratory test results. -Laboratory results outside the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
Participants must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two anti-seizure medications (ASMs) for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving ASMs.
Patients taking psychoactive medication(s) should be on a stable regimen of not more than three such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study. Psychoactive medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
If patients are receiving non-pharmacological, behavioral and/or dietary interventions, they must be stable and have been doing so for three months prior to screening.
Patients have a body mass index between 12-30 kg/m2 (inclusive).
Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures, and in the Investigator's opinion, are reliable and willing and able to comply with all protocol requirements and procedures.
Exclusion Criteria:
Females who are pregnant, nursing or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined below for the duration of therapy and for three months after the last dose of study medication. Standard acceptable methods of contraception include abstinence (defined as refraining from heterosexual intercourse from screening to three months after the last dose of study medication) or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
Patient has transitioned to independent living or living in a residential facility such as a university setting or congregate care.
History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin levels greater than or equal to 2 times the upper limit of normal or alkaline phosphatase levels greater than or equal to 3 times the upper limit of normal.
Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines (except midazolam or comparable administered for blood draws and ECG collection), and opiates.
Patient is using the following AEDs (medications for the treatment of seizures and/ or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin.
Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4 including but not limited to the following medications: midazolam (except single doses administered for the purposes of obtaining blood samples and ECG's), oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, St. John's Wort, and grapefruit Juice/products.
Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECGs) at screening or throughout the study.
Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
Patient has acute or progressive neurological disease, psychosis, schizophrenia or any other psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the study objectives or ability to adhere to protocol requirements.
Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.
Patient has known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or other serious cardiac problems.
Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments or absorption of the trial drug.
History of treatment for, or evidence of, drug abuse within the past year.
Previous participation in a ZYN002 study (with the exception of patients who were screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).
Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study. ZYN002 - transdermal gel, Placebo, ZYN002 - transdermal gel, Placebo
Fragile X Syndrome
Human Genetics and Inherited Disorders, Other human genetics and inherited disorders
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 to old
Phase 3
STUDY00012487
STUDY00012487
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. Inhaled treprostinil solution, Placebo solution, Inhaled treprostinil solution, Placebo solution
Pulmonary Hypertension, Chronic Obstructive Pulmonary Disease
Clinics and Surgery Center (CSC)
Effect and safety of liraglutide 3.0 mg on weight management in children with obesity aged 6 to < 12 years: 56-week, double-blind, randomised, placebo-controlled trial
This study will compare the effect of liraglutide 3.0 mg subcutaneous once daily versus liraglutide placebo on weight management in children aged 6 to <12 years with placebo. The study will also compare the effect of liraglutide 3.0 mg s.c. once daily versus placebo in children aged t to 12 years with obesity on cardiovascular risk factors and metabolism.
Claudia Fox
All
10 Years to 17 Years old
Phase III
STUDY00011812
STUDY00011812
Inclusion Criteria:
Stated willingness to comply with all study procedures and availability for the duration of the study.
Male or female, aged 10-<18 years
BMI ≥ 95th age- and sex-specific Centers for Disease Control (CDC) percentile
Tanner stage ≥ 1
Ability to take oral medication and be willing to adhere to the lifestyle therapy regimen
Exclusion Criteria:
Contraindications to phentermine including: history of cardiovascular disease (including coronary artery disease, stroke, clinically significant congenital heart disease, clinically significant cardiac arrhythmias, congestive heart failure); glaucoma; current or recent (<14 days) use of MAO inhibitors; history of or current chemical dependency; current pregnancy or plans to be pregnant during course of study or lactation; known hypersensitivity to sympathomimetic amines.
Hypertension
Cardiac pacemaker
Type 1 or type 2 diabetes mellitus
Current or recent (<6 months prior to enrollment) use of weight loss medication(s)
Current use of other sympathomimetic amines such as ADHD stimulants
History of bariatric surgery
Schizophrenia, psychosis, or mania
Any history of suicide attempt
Self-harm within 12 months prior to screening
PHQ-9 score of ≥15 at screening
Suicidal ideation of type 4 or 5 on C-SSRS in past month
Hyperthyroidism Lifestyle Management, Lifestyle Management
Obesity, Childhood
Obesity
A Pivotal, Multicenter, Blinded, Sham Procedure-Controlled Trial of Renal Denervation by the Peregrine System Kit, in Subjects with Hypertension (TARGET BP I)
Primary Objective (Randomized Controlled Trial [RCT] Cohort) To evaluate the efficacy of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in uncontrolled hypertensive subjects when used in combination with antihypertensive medications. Primary Efficacy Endpoint Change in mean 24-hour ambulatory systolic blood pressure (SBP) from baseline to 3 months post-procedure. • To evaluate the acute and chronic safety of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in uncontrolled hypertensive subjects when used in combination with antihypertensive medications. • To evaluate the sustained efficacy of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in uncontrolled hypertensive subjects when used in combination with antihypertensive medications. • To evaluate the performance of the Peregrine Kit (co-packaged combination of the alcohol and the Peregrine Catheter) for its intended use.
John Osborn Jr.
All
18 Years to 80 Years old
Phase III
STUDY00014168
STUDY00014168
Inclusion Criteria:
Has 3 office blood pressure measurements with a mean office systolic blood pressure (SBP) of ≥150 mmHg and ≤180 mmHg, AND a mean office diastolic blood pressure (DBP) of ≥90 mmHg when receiving 2 to 5 antihypertensive medications.
Has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings
Exclusion Criteria:
Subject has renal artery anatomy abnormalities.
Subject has an estimated glomerular filtration rate (eGFR) of ≤45 mL/min/1.73 m2, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; or is on chronic renal replacement therapy.
Subject has documented sleep apnea.
Subject has any of the following conditions: severe cardiac valve stenosis, heart failure (New York Heart Association [NYHA] Class III or IV), chronic atrial fibrillation, and known primary pulmonary hypertension (>60 mmHg pulmonary artery or right ventricular systolic pressure).
Subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period (female subjects only).
Subject is being treated chronically (e.g. daily use) with NSAIDs, immunosuppressive medications, or immunosuppressive doses of steroids. Aspirin therapy and nasal pulmonary inhalants are allowed.
Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure. Dehydrated alcohol, Peregrine System Kit (Sham Procedure), Dehydrated alcohol, Peregrine System Kit (Sham Procedure)
Hypertension
Alcohol, Renal Denervation
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects with Classic Congenital Adrenal Hyperplasia
Study SPR001-203 will be a larger, randomized, double-blind, placebo-controlled, dose-ranging study that will investigate the efficacy and safety of up to 52 weeks of treatment with tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline (A4 >1.5x upper limit of normal [ULN] and ACTH >2x ULN) on their current Glucocorticoid regimen.
Kyriakie Sarafoglou
All
18 Years to old
Phase III
STUDY00009488
STUDY00009488
Inclusion Criteria:
Male and female subjects over 18 years old, inclusive
Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented elevated 17-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
Has been on a stable supraphysiologic dose of GC replacement ≥15 mg/day and ≤60 mg/day in HC equivalents
For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening
Exclusion Criteria:
Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21 hydroxylase deficiency)
Has a history that includes bilateral adrenalectomy or hypopituitarism
Has a history of allergy or hypersensitivity to Tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
Current treatment with dexamethasone as GC therapy for CAH. Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for ≥1 month before screening.
Shows clinical signs or symptoms of adrenal insufficiency Tildacerfont/Placebo, Tildacerfont/Placebo
Congenital Adrenal Hyperplasia
Adrenal Disorder, CAH, Congenital Adrenal Hyperplasia
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
STUDY00003568
STUDY00003568
Inclusion Criteria:
Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
Patient must be >= 365 days and =< 30 years of age at diagnosis
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 Autologous Hematopoietic Stem Cell Transplantation, Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Dexrazoxane Hydrochloride, Dinutuximab, Doxorubicin Hydrochloride, Etoposide Phosphate, External Beam Radiation Therapy, Iobenguane I-131, Isotretinoin, Lorlatinib, Melphalan Hydrochloride, Sargramostim, Therapeutic Conventional Surgery, Thiotepa, Topotecan Hydrochloride, Vincristine Sulfate, Autologous Hematopoietic Stem Cell Transplantation, Busulfan, Carboplatin, Cisplatin, Cyclophosphamide, Dexrazoxane Hydrochloride, Dinutuximab, Doxorubicin Hydrochloride, Etoposide Phosphate, External Beam Radiation Therapy, Iobenguane I-131, Isotretinoin, Lorlatinib, Melphalan Hydrochloride, Sargramostim, Therapeutic Conventional Surgery, Thiotepa, Topotecan Hydrochloride, Vincristine Sulfate
Ganglioneuroblastoma, Neuroblastoma
ZEUS - Effects of ziltivekimab versus placebo on cardiovascular outcomes in patients with established atherosclerotic cardiovascular disease, chronic kidney disease and systemic inflammation (ZEUS)
We are doing this study to see if ziltivekimab reduces the risk of having cardiovascular events (for example heart attack and stroke) in people with cardiovascular disease, chronic kidney disease and inflammation. Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). This is known as the study medicine. Which treatment participants get is decided by chance. Participants chance of getting ziltivekimab or placebo is the same. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine doctors cannot prescribe. Participants will get the study medicine in a pre filled syringe. Participants will need to use the pre filled syringe to inject the study medicine into a skinfold once-monthly. The study is expected to last for 2.5 to 4 years. Participants will have up to 20 clinic visits. Participants will have blood and urine samples taken at most of the clinic visits. Participants will have their heart examined using sound waves (echocardiography) and electrodes (electrocardiogram). Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period.
Daniel Duprez
All
18 Years to old
Phase III
STUDY00013843
STUDY00013843
Inclusion Criteria:
Chronic kidney disease defined by one of the below:
Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 15 and below 60 mL/min/1.73 m^2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
Urinary albumin-to-creatinine ratio (UACR) >= 200 milligrams per gram (mg/g) and eGFR >= 60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation)
Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligram per liter (mg/L)
Evidence of atherosclerotic cardiovascular disease (ASCVD) by one or more of the following:
a) Coronary heart disease defined as at least one of the following: i. Documented history of MI ii. Prior coronary revascularisation procedure iii. greater than or equal to 50% stenosis in major epicardial coronary artery documented by cardiac catheterisation or CT coronary angiography b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke of atherosclerotic origin ii. Prior carotid artery revascularisation procedure iii. greater than or equal to 50% stenosis in carotid artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound.
c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an ankle-brachial index (ABI) below or equal to 0.90 at rest ii. Intermittent claudication with a greater than or equal to 50% stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularisation procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis).
Exclusion Criteria:
Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
Myocardial infarction, stroke, hospitalisation for unstable angina pectoris, or transient ischaemic attack within 60 days prior to randomisation (visit 2).
Planned coronary, carotid or peripheral artery revascularisation known on the day of randomisation (visit 2).
Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2). Ziltivekimab, Placebo (ziltivekimab), Ziltivekimab, Placebo (ziltivekimab)
Cardiovascular Risk, Chronic Kidney Disease, Inflammation
Clinics and Surgery Center (CSC)
MT2020-35 - COG AAML1831 - A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations
The overall goal of this study is to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, and to find out what effects, good and/or bad, the drug gilteritinib has when given with chemotherapy to children and young adults with newly diagnosed AML and the FLT3/ITD mutation or non-ITD FLT3 activating mutations.
Peter Gordon
All
to 22 Years old
Phase 3
STUDY00010751
STUDY00010751
Inclusion Criteria:
All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures
Patients must be less than 22 years of age at the time of study enrollment
Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
Patient must have 1 of the following:
>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
ARM C: Patient must be >= 2 years of age at the time of Late Callback
ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
ARM D: Patient must be >= 2 years of age at the time of Late Callback
ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
Fanconi anemia
Shwachman Diamond syndrome
Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
Telomere disorders
Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
Any concurrent malignancy
Juvenile myelomonocytic leukemia (JMML)
Philadelphia chromosome positive AML
Mixed phenotype acute leukemia
Acute promyelocytic leukemia
Acute myeloid leukemia arising from myelodysplasia
Therapy-related myeloid neoplasms
Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
Administration of prior anti-cancer therapy except as outlined below:
Hydroxyurea
All-trans retinoic acid (ATRA)
Corticosteroids (any route)
Intrathecal therapy given at diagnosis
In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
ARM D: Patient does not have any congenital long QT syndrome or congenital heart block Allogeneic Hematopoietic Stem Cell Transplantation, Asparaginase, Asparaginase Erwinia chrysanthemi, Cogstate Assessment Battery, Cytarabine, Daunorubicin Hydrochloride, Dexrazoxane Hydrochloride, Etoposide, Gemtuzumab Ozogamicin, Gilteritinib Fumarate, Liposome-encapsulated Daunorubicin-Cytarabine, Methotrexate, Mitoxantrone Hydrochloride, Therapeutic Hydrocortisone, Allogeneic Hematopoietic Stem Cell Transplantation, Asparaginase, Asparaginase Erwinia chrysanthemi, Cogstate Assessment Battery, Cytarabine, Daunorubicin Hydrochloride, Dexrazoxane Hydrochloride, Etoposide, Gemtuzumab Ozogamicin, Gilteritinib Fumarate, Liposome-encapsulated Daunorubicin-Cytarabine, Methotrexate, Mitoxantrone Hydrochloride, Therapeutic Hydrocortisone
Acute Myeloid Leukemia
A Phase 3 Randomized Controlled Trial of Post-Surgical Stereotactic Radiotherapy (SRT) versus Surgically Targeted Radiation Therapy (STaRT) with Gamma Tile for Treatment of Newly Diagnosed Metastatic Brain Tumors.
Clark Chen
All
18 Years to old
Phase 3
STUDY00012456
STUDY00012456
Inclusion Criteria:
Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
One to four newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
One lesion, designated the index lesion, is planned for surgical resection and is to be between 2.5 cm and 5.0 cm on the screening MRI. Index lesions > 2.0 cm but <2.5 cm are also eligible if surgery is deemed clinically necessary and appropriate for an attempted gross total resection by the neurosurgeon.
Non-index lesions must measure < 4.0 cm in maximal extent on the screening MRI brain scan. The unresected lesions will be treated with SRT as outlined in the treatment section of the concept.
All metastases must be located > 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible.
Previous and/or concurrent treatment with systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) is permitted and must follow protocol guidelines as follows: Systemic therapy is allowed a minimum of one week from last systemic therapy cycle to surgical resection, and one week after surgical resection to allow a minimum of one week before starting/resuming systemic therapy, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Systemic therapy is not allowed 1 day before SRT, the same day as the SRT, or 1 day after the completion of the SRT or longer, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Agents that are delivered by implant or depot injections (such as hormonal therapies) are excluded from these restrictions.
KPS score of ≥70.
Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months.
Ability to complete an MRI of the head with contrast
Adequate renal and hepatic function to undergo surgery, in investigators opinion.
For women of childbearing potential only, a negative urine or serum pregnancy test done < 7 days prior to randomization is required. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period.
Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
Subjects must be fluent in English language to allow for completion of neurocognitive tests and completion of QOL questionnaires. Non-English speaking subjects are not permitted to participate given that participation in the real time integrated neurocognitive function tests is mandatory for all patients. The psychometric properties for translated tests are either not known or not as robust.
Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedures.
Exclusion Criteria
Age <18 years.
KPS<70
Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed as long as any treated lesions are were >15mm from the index lesion.
Patients with >4 newly diagnosed metastases on screening MRI
Pregnant patients.
Primary germ cell tumor, small cell carcinoma, or lymphoma.
Leptomeningeal metastasis (LMD). Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as radiologic or clinical evidence of leptomeningeal involvement with or without positive cerebrospinal fluid (CSF) cytology.
Prior WBRT for brain metastases.
Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
Comorbid psychiatric or neurologic disease or injury impacting cognition, in the opinion of the treating physician, that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
Subjects who, in the investigator's opinion, are unable to understand the protocol or to give informed consent, have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care. Gamma Tile-Surgically Targeted Radiation Therapy (STaRT), Stereotactic Radiation Therapy, Gamma Tile-Surgically Targeted Radiation Therapy (STaRT), Stereotactic Radiation Therapy
Brain Metastases
Clinics and Surgery Center (CSC)
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Pediatric Subjects with Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Pediatric Subjects with Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment Participants will be randomized to placebo or Crinecerfont for 28 weeks followed by an open-label period where all participants will receive Crinecerfont for 24 weeks. The purpose of this research study in children (ages 2 to 17 years) with CAH are: • To study whether crinecerfont can lower high levels of adrenal androgens (male hormones) and high doses of glucocorticoid medication • To study whether improving high androgen levels and high glucocorticoid doses can lead to improvements in CAH • To learn about what happens to crinecerfont in the body by measuring levels in your child’s body after starting the study drug. • To study the safety and tolerability of crinecerfont The study will last for about 60 weeks with 14 study visits. The main activities in this study are: physical exams, height and weight measurements, vital signs, study drug dosing, glucocorticoid dose adjustments, blood draws, saliva and urine tests, electrocardiogram (ECG) testing, x-ray for bone age, ultrasound of testes (boys), and questionnaires.
Kyriakie Sarafoglou
All
2 Years to 17 Years old
Phase III
STUDY00012858
STUDY00012858
Inclusion Criteria:
Be willing and able to adhere to the study procedures, including all requirements at the study center, and return for the follow-up visit.
Have a medically confirmed diagnosis of 21-hydroxylase deficiency CAH.
Be on a stable regimen of steroidal treatment for CAH.
Have elevated androgen levels.
Participants of childbearing potential must be abstinent or agree to use appropriate birth control during the study.
Exclusion Criteria:
Have a diagnosis of any of the other forms of classic CAH.
Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy.
Have a clinically significant unstable medical condition or chronic disease other than CAH.
Have a history of cancer unless considered to be cured.
Have a known history of clinically significant arrhythmia or abnormalities on ECG.
Have a known hypersensitivity to any corticotropin-releasing hormone antagonist.
Have received an investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study.
Have current substance dependence or substance (drug) or alcohol abuse.
Have had a significant blood loss or donated blood or blood products within 8 weeks prior to the study. Crinecerfont, Placebo, Crinecerfont, Placebo
Congenital Adrenal Hyperplasia
21-hydroxylase deficiency, classic congenital adrenal hyperplasia (CAH)
COG ACNS1833 - A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine versus Selumetinib (NSC# 748727, IND# 77782) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) not associated with BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)
The overall goal of this phase 3 non-inferiority study is to assess if selumetinib works as well as the standard treatment using carboplatin and vincristine (called CV) for subjects with low-grade glioma (LGG).
Christopher Moertel, MD
All
2 Years to 21 Years old
Phase 3
STUDY00009277
STUDY00009277
Inclusion Criteria:
Patients must be >= 2 years and =< 21 years at the time of enrollment
Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
Patients with metastatic disease or multiple independent primary LGG are eligible
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):
Age: Maximum Serum Creatinine (mg/dL)
2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
>= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications)
Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Patients must have the ability to swallow whole capsules
All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
All patients and/or their parents or legal guardians must sign a written informed consent
All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
Patients may not be receiving any other investigational agents
Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants are not eligible
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
Symptomatic heart failure
New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
Severe valvular heart disease
History of atrial fibrillation
Current or past history of central serous retinopathy
Current or past history of retinal vein occlusion or retinal detachment
Patients with uncontrolled glaucoma
If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
Note: Patients must have healed from any prior surgery
Patients who have an uncontrolled infection are not eligible Biospecimen Collection, Carboplatin, Magnetic Resonance Imaging, Quality-of-Life Assessment, Questionnaire Administration, Selumetinib Sulfate, Vincristine Sulfate, Biospecimen Collection, Carboplatin, Magnetic Resonance Imaging, Quality-of-Life Assessment, Questionnaire Administration, Selumetinib Sulfate, Vincristine Sulfate
Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma
A double blind, randomized, placebo-controlled trial evaluating the efficacy and safety of BI 1015550 over at least 52 weeks in patients with Idiopathic Pulmonary Fibrosis (IPF)
The purpose of this trial is to evaluate the efficacy, safety, and tolerability of BI 1015550 9 mg bid and 18 mg bid compared to placebo in patients with IPF in addition to patient’s standard of care over the course of at least 52 weeks. New treatments with better tolerability are needed for patients with IPF to further reduce the decline in lung function and improve quality of life. Based on its anti-inflammatory and antifibrotic properties and the preliminary clinical evidence described, BI 1015550 may provide an additional treatment option to patients with pulmonary fibrosis irrespective of concomitant treatment with standard of care.
Hyun Kim
All
40 Years to old
Phase III
STUDY00016653
STUDY00016653
Inclusion criteria
Patients ≥40 years old at the time of signed informed consent.
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
Diagnosis of Idiopathic Pulmonary Fibrosis (IPF)
Patients may be either:
on a stable therapy* with nintedanib or pirfenidone for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. Combination of nintedanib plus pirfenidone is not allowed. (*stable therapy is defined as the individually and general tolerated regimen of either nintedanib or pirfenidone (no dose changes) for at least 12 weeks.)
not on a treatment with nintedanib or pirfenidone for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment.
Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1.
Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) corrected for Haemoglobin (Hb) [Visit 1] ≥25% and <90% predicted of normal at Visit 1.
Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control. Of note, oral hormonal contraceptives are not considered a highly effective method due to potential drug-drug interactions.
Exclusion criteria
Relevant airways obstruction (prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced vital capacity (FVC) <0.7) at Visit 1.
In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
Acute Idiopathic Pulmonary Fibrosis (IPF) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined).
Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not fully recovered according to investigator judgement within the 4 weeks prior to randomization (Visit 2).
Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery.
Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) >2.5 x Upper limit of normal (ULN) or total Bilirubin >1.5 x ULN at Visit 1.
Further exclusion criteria apply.
BI 1015550, Placebo, BI 1015550, Placebo
Idiopathic Pulmonary Fibrosis
Clinics and Surgery Center (CSC)
Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Specific Aims: Specific Aim 1: Determine whether a three-month course of daily brivaracetam reduces below-level neuropathic pain in SCI. The objective of this aim is to assess efficacy of a three-month course of brivaracetam to reduce neuropathic pain in men and women with SCI. We will assess change in pain intensity and related outcomes, including mood, satisfaction with life, and community integration. We will monitor drug adverse events and tolerability. Specific Aim 2: Determine whether a three-month course of daily brivaracetam increases parietal operculum brain connectivity. The objective of this exploratory aim is to assess the effect of a three-month course of brivaracetam treatment on parietal operculum activation and connectivity in SCI. We will assess changes in cortical activity of related pain perception regions and networks in the brain in response to brivaracetam treatment compared to placebo using rsfMRI and pain-related task-based fMRI. To achieve this aim, we will test the working hypothesis that brivaracetam increases parietal operculum activation and connectivity compared to placebo, using rsfMRI, task-based fMRI, and a validated image processing protocol. We will also examine changes in network connectivity and brain activity in the insula, because of its concurrent reported importance for neuropathic pain in SCI. We will assess the association between functional connectivity of the parietal operculum and the insula and change in pain intensity in response to brivaracetam treatment. Specific Aim 3: Determine whether baseline microRNA-485 levels are associated with response to brivaracetam treatment. The objective of this exploratory aim is to assess microRNA expression as a potential predictive biomarker of response to brivaracetam treatment. To achieve this, we will test the working hypothesis that baseline circulating miR-485 levels predict change in pain intensity in response to brivaracetam treatment. To test this, we will use Next-Generation sequencing. We will assess miR-485 levels at baseline and after a three-month treatment course.
Ricardo Battaglino
All
18 Years to old
Phase 3
STUDY00015302
STUDY00015302
Inclusion Criteria:
18 years of age or older
Injured for > 3 months
Completed inpatient rehabilitation and living in the community
Chronic sublesional neuropathic pain defined as persistent pain (VAS grade 3-10) for three months or more
For people of child-bearing potential: currently practicing an effective form of two types of birth control (defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly).
Exclusion Criteria:
Progressive myelopathy secondary to posttraumatic cord tethering or syringomyelia
Active use of drugs known to interact with brivaracetam: rifampin, carbamazepine, sodium oxybate, buprenorphine, propoxyphene, levetiracetam, and phenytoin.
Brain injury or cognitive impairment limiting the ability to follow directions or provide informed consent
Pregnancy or lactation
Epilepsy or active treatment for seizure disorder
Past or current suicidality
Active treatment for psychiatric disease
Drug addiction
Moderate or heavy alcohol intake (up to four alcoholic drinks for men and three for women in any single day, and a maximum of 14 drinks for men and 7 drinks for women per week)
Hepatic cirrhosis, Child-Pugh grades A, B, and C
Impaired renal function (GFR<60ml/minute)
Contraindications to brivaracetam or pyrrolidine derivatives including allergy
Active clinically significant disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrine, psychiatric, hematologic, urologic, or other acute or chronic illness) that, in the opinion of the investigator, would make the patient an unsuitable candidate for this trial.
History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of brivaracetam
Use of any investigational drug 30 days prior to enrollment in this study
Enrollment in another clinical trial. brivaracetam, Placebo, brivaracetam, Placebo
Spinal Cord Injuries, Neuropathic Pain
An Open-Label Long-term Follow-up Study to Evaluate the Effects of Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH (SOTERIA)
This Phase 3 study is being conducted to assess the long-term safety, tolerability, and efficacy of sotatercept in PAH. Long-term followup of patients receiving sotatercept is important to understand the maintenance and durability of treatment effect (especially in the presence of background PAH therapy) and to provide greater opportunity for pharmacovigilance following sotatercept treatment in the selected patient populations. This LTFU study is supported by data from the PULSAR study (Phase 2, NCT03496207), in which treatment with sotatercept resulted in hemodynamic and functional improvements in the study participants, including those receiving maximal PAH therapy with double/triple drug combinations and intravenous prostacyclin.
Thenappan Thenappan
All
18 Years to old
Phase 3
STUDY00016119
STUDY00016119
Inclusion Criteria:
Participants must have completed their current respective PAH sotatercept clinical study and its requirements, and must not have discontinued early.
Participants must be willing to adhere to the study visit schedule and understand and comply with all protocol requirements.
Participants must have the ability to understand and provide documented informed consent.
Females 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 in combination with a barrier method 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.
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.
Participants must agree not to participate in any other trials of investigational drugs/devices while they are enrolled in the A011-12 study.
Exclusion Criteria:
Not enrolled in a PAH parent study at the time of enrollment.
Missed more than the equivalent of 4 consecutive doses between the end of parent study and the start of this study.
Presence of an ongoing serious adverse event that occurred during a PAH sotatercept clinical study that is assessed to be possibly or probably related to sotatercept.
Pregnant or breastfeeding females. Sotatercept, Sotatercept
Pulmonary Arterial Hypertension, PAH
Clinics and Surgery Center (CSC)
Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS- RCT) (CHASM-CS-RCT)
This is a Prospective, open-label, non-inferiority, randomized controlled trial (1:1 randomization) with blinded end-point analysis comparing the use of Prednisone versus Prednisone plus Methatrexate in the treatment of Cardiac Sarcoidosis.
Chetan Shenoy
All
18 Years to old
Phase III
STUDY00015181
STUDY00015181
Inclusion Criteria:
(i) Cardiac sarcoidosis presenting with one or more of the following clinical findings:
advanced conduction system disease (defined as Mobitz II AV block or third degree AV block)
significant sinus node dysfunction (defined as average HR less than 40bpm when awake and/or sustained atrial arrhythmias)
non- sustained or sustained ventricular arrhythmia
left ventricular dysfunction (LVEF < 50%)
right ventricular dysfunction (RVEF < 40%)
AND
(ii) No alternative explanation for clinical features
AND
(iii) FDG-PET uptake suggestive of active CS within two months of enrollment (confirmed by PET core lab read)
AND ONE OR BOTH OF FOLLOWING
(iv) Positive biopsy for Sarcoid (either EMB or extra-cardiac)
(v) CT Chest showing features consistent with pulmonary sarcoidosis and/or mediastinal and/or hilar lymphadenopathy
Exclusion Criteria:
Current or recent (within two months) non-topical treatment for sarcoidosis
Currently taking Methotrexate or Prednisone for another health condition
Intolerance or contra-indication to Methotrexate or Prednisone
Patient does not meet all of the above listed inclusion criteria
Patient is unable or unwilling to provide informed consent
Patient is included in another randomized clinical trial
Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
Breastfeeding
Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
Patients for whom the investigator believes that the trial is not in the interest of the patient Prednisone or Prednisolone, Methotrexate, Prednisone or Prednisolone, Methotrexate
Cardiac Sarcoidosis, Sarcoidosis
Cardiac Sarcoidosis, Methotrexate, Prednisone (or Prednisolone)
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Intravenous Efzofitimod in Patients with Pulmonary Sarcoidosis
This is a multicenter, randomized, double-blind, placebo-controlled, study comparing the efficacy and safety of intravenous (IV) efzofitimod 3 mg/kg and 5 mg/kg versus placebo after 48 weeks of treatment. This study will enroll adults with histologically confirmed pulmonary sarcoidosis receiving stable treatment with oral corticosteroid (OCS), with or without immunosuppressant therapy.
Maneesh Bhargava
Male or Female
18 Years and over
STUDY00016463
STUDY00016463
Inclusion Criteria:
Confirmed diagnosis of pulmonary sarcoidosis for at least 6 months, defined by the following criteria: documented histologically proven diagnosis of sarcoidosis by tissue biopsy and documented evidence of parenchymal lung involvement by historical radiological evidence
Evidence of symptomatic pulmonary sarcoidosis, as demonstrated by the following criteria: Modified Medical Research Council (MRC) dyspnea scale grade of at least 1 and KSQ-Lung score ≤70
Patients must be receiving treatment with OCS of ≥ 3 months with a starting dose between ≥ 7.5 and ≤ 25 mg/day.
Body weight ≥ 40 kg and < 160 kg
Exclusion Criteria:
Treatment with > 1 oral immunosuppressant therapy
Treatment with biological immunomodulators, such as tumor necrosis factor-alpha (TNF-α) inhibitors or antifibrotics or interleukin inhibitors
Likelihood of significant pulmonary fibrosis as shown by any 1 or more of the following: High resolution CT fibrosis > 20% within the last 12 months; FVC percent predicted (FVCPP) < 50% and KSQ-Lung score < 30
Clinically significant pulmonary hypertension requiring treatment with vasodilators
Patients with cardiac sarcoidosis, neurosarcoidosis, or renal sarcoidosis
Clinically significant cutaneous and ocular sarcoidosis
History of Addisonian symptoms that precluded previous OCS taper attempts
Is an active, heavy smoker of tobacco/nicotine-containing products
History of anti-synthetase syndrome or Jo-1 positive at baseline Efzofitimod 3 mg/kg, Efzofitimod 5 mg/kg, Placebo, Efzofitimod 3 mg/kg, Efzofitimod 5 mg/kg, Placebo
Rare Diseases, Breathing, Lung & Sleep Health, Respiratory System
Clinics and Surgery Center (CSC), Sarcoidosis
COG ARST2031: A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy with Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) plus VINO-CPO Maintenance in Patients with High Risk Rhabdomyosarcoma (HR-RMS)
his phase III trial compares the safety and effect of adding vinorelbine to vincristine, dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after treatment or spread to other parts of the body. This study will also examine if adding maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in a class of medications called vinca alkaloids. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy. Cyclophosphamide is in a class of medications called alkylating agents. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are chemotherapy medications that work by slowing or stopping the growth of cancer cells in the body. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or for the rest of patient's life.
Emily Greengard
All
to 50 Years old
STUDY00017650
STUDY00017650
Inclusion Criteria:
Patients must be =< 50 years of age at the time of enrollment
Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon stage, group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
ERMS
Stage 4, group IV, >= 10 years of age
ARMS
Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
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 (must be performed within 7 days prior to enrollment):
Age; Maximum serum creatinine (mg/dL)
1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
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 evidence of uncontrolled infection are not eligible
RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
Patients with central nervous system involvement of RMS as defined below:
Malignant cells detected in cerebrospinal fluid
Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
Diffuse leptomeningeal disease
Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
Note: the following exception:
Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment
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 Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Bone Scan, Computed Tomography, Cyclophosphamide, Dactinomycin, Magnetic Resonance Imaging, Positron Emission Tomography, Radiation Therapy, Vincristine Sulfate, Vinorelbine Tartrate, X-Ray Imaging, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Bone Scan, Computed Tomography, Cyclophosphamide, Dactinomycin, Magnetic Resonance Imaging, Positron Emission Tomography, Radiation Therapy, Vincristine Sulfate, Vinorelbine Tartrate, X-Ray Imaging
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma
A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of 177Lu-PSMA-I&T versus Hormone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.
This is a prospective, randomized, open-label, multicenter Phase 3 study evaluating the efficacy and safety of 177Lu-PSMA-I&T versus a switch in standard of care hormone therapy in men with metastatic castration-resistant prostate cancer (mCRPC)
Gautam Jha
Male
18 Years to old
Phase III
STUDY00014801
STUDY00014801
Inclusion Criteria:
Male 18 years or older able to understand and provide signed written informed consent.
Histologically or pathologically confirmed prostate adenocarcinoma without predominant small cell component.
Progressive disease by one or more of the following criteria:
Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL.
Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria).
Previous treatment with next-generation androgen receptor (AR)-directed therapy (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).
Must have received no more than one previous AR-directed therapy.
Must have been administered ARAT (abiraterone, enzalutamide, darolutamide, or apalutamide) in the castration-sensitive or castration-resistant setting.
Must have progressed while on ARAT.
PSMA-PET scan (e.g., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by central reader.
Effective castration with serum testosterone level of <50 ng/dL and plan to continue with chronic medical or surgical castration.
Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
Patients with HIV that are healthy and with a low risk of acquired immune deficiency syndrome related outcomes may participate in the trial at the investigators' discretion.
Patients with HBV and HCV may also participate if symptoms are sufficiently managed.
Life expectancy of at least 6 months as assessed by investigator.
Willing to initiate ARAT therapy determined by investigator.
For patients who have partners of childbearing potential: The patient and/or partner must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after the last study drug administration.
Exclusion Criteria:
Prior treatment with radioligand therapy including other lutetium-labeled compounds.
Prior treatment with radium-223 (Xofigo) within the past 12 weeks.
Prior chemotherapy treatment for castration-resistant prostate cancer. Prior docetaxel use in the hormone-sensitive setting is permitted, as long as no more than 6 doses were received, the last dose was administered >1 year prior to consent, and disease progression did not occur during docetaxel treatment.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2
Patients with known HRR gene-mutation who have not been previously treated with olaparib or rucaparib.
Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
Inadequate organ and bone marrow function as evidenced by:
Hemoglobin < 8 g/dL.
Absolute neutrophil count < 1.5 x 109/L.
Platelet count < 100 x 109/L.
AST/SGOT and/or ALT/SGPT > 3.0 x ULN.
Total bilirubin > 2 x ULN unless patient has known Gilbert's syndrome and then may be 3 x ULN.
Creatinine clearance (CrCl) < 50 mL/min based on the Cockcroft-Gault equation.
Albumin ≤ 2.75 g/dL
Patients who undergo a transfusion for the sole purpose of meeting eligibility for this trial will be excluded.
Assessment by the Investigator as unable or unwilling to comply with the requirements of the protocol.
Use of an investigational therapeutic drug within the last 4 weeks prior to start of study treatment or scheduled to receive one during the study period.
Known CNS metastasis unless received therapy, asymptomatic and neurologically stable.
Patients receiving zoledronic acid for bone-targeted therapy must be on stable dose for 4 weeks prior to randomization.
Major surgery within 30 days of randomization as determined by the Investigator.
Patients with active significant cardiac disease defined by any of the following:
New York Heart Association class 3 or 4 congestive heart failure within 6 months of signing the ICF unless treated with improvement.
Current diagnosis of electrocardiogram abnormalities with significant cardiac arrhythmias
History of long QT syndrome or know history of Torsades de Pointe
History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months of ICF signature
Participants with symptomatic cord compression or clinical/radiological findings indicating impending spinal cord compression
Patients with a superscan seen on baseline bone scan as determined by investigator.
Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
Previous use of G-CSF for persistent neutropenia after standard of care treatment.
Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy.
Participants with active Covid19. Recovered patients may be included when completely recovered (no symptoms at least 28 days before study medication and a negative Covid test within 72 hours). 177Lu-PSMA-I&T, Abiraterone with Prednisone or Enzalutamide, 177Lu-PSMA-I&T, Abiraterone with Prednisone or Enzalutamide
Metastasis From Malignant Tumor of Prostate
Clinics and Surgery Center (CSC)
PSMAddition: An International Prospective Open-label, Randomized, Phase III Study comparing 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC) (PSMAddition)
To evaluate radiographic progression free survival in patients with mHSPC receiving Standard of Care and 177Lu-PSMA-617 versus patients receiving Standard of Care without 177Lu-PSMA-617.
Emmanuel Antonarakis
Male
18 Years to old
Phase 3
STUDY00015038
STUDY00015038
Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
Signed informed consent must be obtained prior to participation in the study
Patients must be adults ≥18 years of age
Patients must have an ECOG performance status of 0 to 2
Patients must have a life expectancy >9 months as determined by the study investigator
Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
Patients must have adequate organ function:
Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
Albumin ≥2.5 g/dL
Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
Patients must be:
Treatment naïve OR minimally treated with:
Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.
Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for inclusion in this study.
Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
Ongoing participation in any other clinical trial
Use of other investigational drugs within 30 days prior to day of randomization
Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
Transfusion for the sole purpose of making a participant eligible for study inclusion
Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
Active clinically significant cardiac disease defined as any of the following:
NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.
History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
History of familial long QT syndrome or known family history of Torsades de Pointes
Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
Any condition that precludes raised arms position
Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF 177Lu-PSMA-617, 68Ga-PSMA-11, ARDT, ADT, 177Lu-PSMA-617, 68Ga-PSMA-11, ARDT, ADT
Prostatic Neoplasms
Clinics and Surgery Center (CSC)
AOST2031: A Phase 3 Randomized Controlled Trial Comparing Open vs Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.
Emily Greengard
All
to 50 Years old
Phase 3
STUDY00016802
STUDY00016802
Inclusion Criteria:
Patients must be < 50 years at the time of enrollment.
Patient must have eligibility confirmed by rapid central imaging review.
Patients must have =< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
Patients must have a histological diagnosis of osteosarcoma.
Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
Newly diagnosed patients must be receiving systemic therapy considered by the treating physician as at least equivalent to methotrexate, doxorubicin and cisplatin (MAP) at the time of enrollment on this study.
Patients at time of 1st recurrence must have previously completed initial systemic therapy for their primary tumor, considered by the treating physician as at least equivalent to MAP.
Exclusion Criteria:
Patients with unresectable primary tumor.
Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
Patients with pleural or mediastinal based metastatic lesions, or with pleural effusion.
Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
Patients with evidence of extrapulmonary metastatic disease.
Patients who received pulmonary surgery for lung metastasis prior to enrollment.
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. Questionnaire Administration, Thoracoscopy, Thoracotomy, Questionnaire Administration, Thoracoscopy, Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma