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Feasibility Study of the Intravascular Ventricular Assist System (iVAS)
This is a single-arm, non-randomized study designed to assess the preliminary safety and clinical performance of the NuPulseCV iVAS. This study will assess potential benefits to patients who have NYHA Class III and IV advanced heart failure and require additional circulatory support. Data obtained from the study will be used to make device modifications, refine the criteria for defining the target population, and inform the design of a future clinical trial suitable for assessing longer-term use in heart failure patients.
Ranjit John
All
18 Years and over
N/A
NCT02645539
STUDY00004194
Main
• At least 18 years of age.
• If female, are postmenopausal or surgically sterilized, or have a negative pregnancy test within seven (7) days of invasive testing.
• Advanced heart failure (NYHA Class III or IV) Main
• Hypotension treated with the following medications: epinephrine, norepinephrine, vasopressin, methylene blue, phenylephrine, or angiotensin II.
• Receiving more than two inotropes.
• Subclavian stenosis or stent.
• Currently receiving circulatory support including ECMO, Impella, TandemLife or equivalents; or any durable VAD.
• Atrial fibrillation without ventricular pacing.
• Concomitant, non-cardiac disease process with life expectancy < 1 year.
• Significant abnormalities of the aorta, such as aneurysms, coarctation of the aorta, or an extremely tortuous aorta.
• Severe end-organ dysfunction or failure.
• Any other condition the heart team believes inappropriate for this study.
Inclusion Criteria:
• At least 18 years of age.
• If female, are postmenopausal or surgically sterilized, or have a negative pregnancy test within seven (7) days of invasive testing.
• Advanced heart failure (NYHA Class III or IV) Main
Exclusion Criteria:
• Hypotension treated with the following medications: epinephrine, norepinephrine, vasopressin, methylene blue, phenylephrine, or angiotensin II.
• Receiving more than two inotropes.
• Subclavian stenosis or stent.
• Currently receiving circulatory support including ECMO, Impella, TandemLife or equivalents; or any durable VAD.
• Atrial fibrillation without ventricular pacing.
• Concomitant, non-cardiac disease process with life expectancy < 1 year.
• Significant abnormalities of the aorta, such as aneurysms, coarctation of the aorta, or an extremely tortuous aorta.
• Severe end-organ dysfunction or failure.
• Any other condition the heart team believes inappropriate for this study.
Device: intravascular ventricular assist system (iVAS)
Heart Failure NYHA Class III, Heart Failure NYHA Class IV
Heart failure, Bridge-to-transplant, circulatory support, VAD, IABP, Clinics and Surgery Center (CSC)
The Organ Care System (OCS) Lung Thoracic Organ Perfusion (TOP) Post Approval Study (PAS) Registry - OCS Lung TOP PAS Registry (TOP)
To collect additional real-world safety and effectiveness data for the OCS™ Lung System and to expand the long-term clinical evidence supporting the use of OCS™Lung System in lung transplantation.
Stephen Huddleston
All
18 Years and over
NA
NCT03639025
STUDY00003837
This is an all-comers registry that will enroll all:
• Consented patients who receive OCS™ preserved double lung transplants from either standard criteria donors or donors initially deemed unacceptable; and
• Consented patients who receive a single lung transplant from OCS™ preserved lung pairs from either standard criteria donors or donors initially deemed unacceptable; and
• All donor lungs that were perfused on OCS Lung System. Enrolled patients will fall into one of the following three possible analysis categories:
• TOP SCDL PAS Primary Analysis Population: will be comprised of the first 289 eligible/PAS consented recipients transplanted with SCDL primary analysis population eligible donor lungs preserved on the OCS™ Lung System.
• TOP DLIDU Primary Analysis Population: Will be comprised of the first 266 eligible/PAS consented recipients transplanted with DLIDU primary analysis population eligible donor lungs preserved on the OCS™ Lung System.
• All Other Enrolled Patients: will be comprised of all OCS Lung transplanted patients in the TOP Registry that do not meet any of the above analysis populations.
• Consented patients who receive OCS™ preserved double lung transplants from either standard criteria donors or donors initially deemed unacceptable; and
• Consented patients who receive a single lung transplant from OCS™ preserved lung pairs from either standard criteria donors or donors initially deemed unacceptable; and
• All donor lungs that were perfused on OCS Lung System. Enrolled patients will fall into one of the following three possible analysis categories:
• TOP SCDL PAS Primary Analysis Population: will be comprised of the first 289 eligible/PAS consented recipients transplanted with SCDL primary analysis population eligible donor lungs preserved on the OCS™ Lung System.
• TOP DLIDU Primary Analysis Population: Will be comprised of the first 266 eligible/PAS consented recipients transplanted with DLIDU primary analysis population eligible donor lungs preserved on the OCS™ Lung System.
• All Other Enrolled Patients: will be comprised of all OCS Lung transplanted patients in the TOP Registry that do not meet any of the above analysis populations.
Device: OCS Lung System
Lung Transplantation
Clinics and Surgery Center (CSC)
Sleep SMART: Sleep for Stroke Management And Recovery Trial (Sleep SMART)
Investigator-initiated, phase 3 multicenter, prospective randomized open-, blinded-endpoint (PROBE) controlled trial to test whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure is effective for secondary prevention and recovery after stroke.
Kamakshi Lakshminarayan
All
18 Years and over
N/A
NCT03812653
STUDY00006842
Inclusion Criteria:
• TIA with ABCD2 ≥4 or ischemic stroke, within the prior 14 days.
Exclusion Criteria:
• pre-event inability to perform all of own basic ADLs
• unable to obtain informed consent from subject or legally authorized representative
• incarcerated
• known pregnancy
• current mechanical ventilation (can enroll later if this resolves) or tracheostomy
• current use of positive airway pressure, or use within one month prior to stroke
• anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
• severe bullous lung disease
• history of prior spontaneous pneumothorax or current pneumothorax
• hypotension requiring current treatment with pressors (can enroll later if this resolves)
• other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP
• massive epistaxis or previous history of massive epistaxis
• cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus
• recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure
• current receipt of oxygen supplementation >4 liters per minute
• current contact, droplet, respiratory/airborne precautions
Device: CPAP
Ischemic Stroke, Sleep Apnea, Sleep Apnea, Obstructive, TIA, Stroke, CPAP, Telemedicine, Home Sleep Apnea Test, Randomized Clinical Trial, Multicenter Trial
Effects of cystic fibrosis and cystic fibrosis related diabetes on brain structure and cognitive function
This is an observational cohort study in which patients with cystic fibrosis and healthy controls will undergo one research MRI to test cognitive function and map brain structures.
Amir Moheet
All
18 Years and over
NA
NCT03820349
STUDY00002606
Inclusion Criteria:
patients with Cystic fibrosis
Exclusion Criteria:
• History of stroke
• History of epilepsy
• History of neurosurgical procedures
• Past or current history of severe psychiatric illness
• Pass or current history of alcohol or substance abuse
• Presence of metallic substances in body or inability to remove before imaging procedure
• History of claustrophobia or known inability to tolerate MRI
• Current pregnancy
• Inability to consent
Cystic Fibrosis
CFRD, Cystic fibrosis
HM2017-39 Phase III Randomized Study of Crenolanib versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects with FLT3 Mutated Acute Myeloid Leukemia
This study is meant to compare the efficacy of crenolanib with midostaurin administered following induction chemotherapy and consolidation therapy on event-free survival (EFS) in newly diagnosed acute myeloid leukemia subjects with FLT3 mutation.
Mark Juckett
All
18 Years to 60 Years old
Phase 3
NCT03258931
STUDY00002581
Inclusion Criteria:
• Confirmed diagnosis of de novo AML according to World Health Organization (WHO) 2016 classification
• Presence of FLT3-ITD and/or D835 mutation(s) in bone marrow or peripheral blood
• Age ≥ 18 years and ≤ 60 years
• Adequate hepatic function within 48 hours prior to induction chemotherapy
• Adequate renal functions within 48 hours prior to induction chemotherapy
• ECOG performance status within 48 hours prior to induction chemotherapy ≤ 3
• Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy specified
Exclusion Criteria:
• Acute promyelocytic leukemia (APL)
• Known clinically active central nervous system (CNS) leukemia
• Severe liver disease
• Active infections
• Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Known infection with human immunodeficiency virus (HIV)
• Prior systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents)(except for hydroxyurea and/or leukapheresis)
Drug: Crenolanib, Drug: Midostaurin, Drug: Cytarabine, Drug: Duanorubicin
Newly Diagnosed FLT3 Mutated AML
Clinics and Surgery Center (CSC)
HYDROXYCHLOROQUINE (HCQ) FOR PREVENTION OF ABNORMAL GLUCOSE TOLERANCE AND DIABETES IN RELATIVES AT-RISK FOR TYPE 1 DIABETES MELLITUS (Protocol TN-22) (TN-22)
The study is a 2-arm, double blinded, multicenter, 2:1 randomized, placebo-controlled clinical trial. All participants will receive close monitoring for progression of T1D. Participants will receive hydroxychloroquine or placebo and close monitoring for progression to Stage 2 (abnormal glucose tolerance) or Stage 3 (clinically overt) T1D. To assess the efficacy, safety and mode of action of hydroxychloroquine to prevent progression from Stage 1 to Stage 2 or Stage 3 of T1D.
Antoinette Moran
All
3 Years and over
Phase 2
NCT03428945
STUDY00004135
Inclusion Criteria:
• Participant in TrialNet Pathway to Prevention Study (TN01)
• Age 3 years or greater at the time of randomization
• Willing to provide informed consent
• Normal glucose tolerance by OGTT within 7 weeks (no more than 52 days) of baseline
• Two or more diabetes-related autoantibodies present on two separate samples
• Weight of 12 kg or greater at screening
• If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and at each study visit
• Anticipated ability to swallow study medication.
Exclusion Criteria:
• Abnormal Glucose Tolerance or Diabetes
• History of treatment with insulin or other diabetes therapies
• Ongoing use of medications known to influence glucose tolerance
• Ongoing or anticipated future use of medications known to have untoward interactions with hydroxychloroquine
• Known hypersensitivity to 4-aminoquinoline compounds
• G6PD deficiency
• History of retinopathy
• Have an active infection at time of randomization
• Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection
• Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
• Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
• Be pregnant or breastfeeding.
Drug: Hydroxychloroquine, Drug: Placebo
Type1 Diabetes Mellitus
TrialNet
SGLT2 Inhibitors as a Novel Treatment for Pediatric Non-Alcoholic Fatty Liver Disease
This is a pilot drug study to evaluate the feasibility and obtain a preliminary estimate of efficacy and safety of the SGLT2 inhibitor, empagliflozin, in adolescents with obesity (BMI-percentile ≥95th) who have MRI-confirmed NAFLD (hepatic fat fraction ≥ 5.5%) and have normal fasting glucose. We will examine changes in body composition, arterial stiffness, biomarkers of fatty liver disease, and insulin sensitivity over 26-weeks.
Justin Ryder
All
12 Years to 17 Years old
Phase 2
NCT03867487
STUDY00003825
Inclusion Criteria:
For clinical referral to screening visit:
• Age: 12 to <20 years old
• Diagnosis of Obesity: BMI-percentile ≥95th (using age- and sex- based Center for Disease Control definitions) or BMI ≥30 kg/m2
• Elevated alanine aminotransferase (ALT) more than twice the upper limit of normal by gender (≥44 U/L for girls, ≥50 U/L for boys) within 3 months prior to screening (used for historic ALT value) OR diagnosis of NAFLD from ultrasound, MRI, or participants with biopsy-proven NASH within 12 moths of screening
• History of lifestyle modification to treat obesity or NAFLD To be obtained at screening visit:
• Confirmation of Obesity
• Tanner stage 2
• Normal fasting glucose tolerance (fasting blood glucose <100 mg/dL)
• If Screening ALT is used as inclusion criteria [if > 2x historic ALT value (historical value obtained clinically within 12 months of screening visit), repeated after 4 weeks [unable to randomize until completed]]. If the repeat ALT is more than 50% increased or decreased over the screening ALT, a third ALT should be obtained. If a third ALT is not within 50% of the previous value, then the subject is ineligible but may be screened at a later date. If ALT is not used:
• An ultrasound will be done to diagnose NAFLD if the diagnosis has not previously been made by ultrasound, MRI or biopsy
• A MRI-derived HFF ≥ 5.5%
• Willingness to adhere to lifestyle considerations throughout the study
Exclusion Criteria:
• ALT > 250U/L at screening
• History of significant alcohol intake or current use
• Impaired fasting glucose (>100 mg/dL)
• Diabetes (type 1 or 2)
• Current or recent (<6 months prior to enrollment) use of weight loss medication(s)
• Vitamin E supplementation
• Previous bariatric surgery
• Use of metformin
• Prior use of empagliflozin
• Lower limb infection/ulceration within 3 months of screening
• Metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible
• Structural and functional urogenital abnormalities, that predispose for urogenital infections
• Recent initiation (<3 months prior to enrollment) of anti-hypertensive or lipid medication(s)
• Major psychiatric disorder
• Current pregnancy or plans to become pregnant.Females unwilling to be tested for pregnancy. Females will be tested for pregnancy. Females who are sexually active and not protected by an effective method of birth control (e.g. UID or medication or patch)
• Tobacco use
• Significant liver dysfunction (levels >5 times the upper limit of normal (ULN)): ALT (ULN = 50 U/L) AST (ULN = 48 U/L) GGT (ULN = 48 U/L) ALP (ULN = 115 U/L)
• Platelets < 150,000 cells/mm3
• Total bilirubin 1.3 mg/dL
• INR 1.3
• Albumin <3.2 g/dL
• Gilbert's Syndrome
• Any known causes of liver disease (except NAFLD and NASH)
• Significant renal dysfunction (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2),
• Diagnosed monogenic obesity
• History of cancer
• Untreated thyroid disorder
• History of decompensation events (ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma)
• Current or recent (<6 months prior to enrollment) use of medication(s) associated with weight gain (e.g. atypical anti-psychotics)
Drug: Empagliflozin 10 MG, Drug: Placebo Oral Tablet
Non-Alcoholic Fatty Liver Disease, NAFLD, Pediatric NAFLD
A closed-loop assessment and treatment platform for unipolar depression and anxiety
This study is a validation study to evaluate the acceptability and feasibility of the closed-loop strategy employing the mobile mental health application with the target population to prepare for a large-scale efficacy trial in adults with MDD, depression and/or anxiety.
Gamze Camsari
All
18 Years to 60 Years old
N/A
NCT02948036
STUDY00004179
Inclusion Criteria:
• Participant must be 18 to 60 years of age.
• Participant must score ≥ 9 on the Patient Health Questionnaire-9 (PHQ-9).
• Participant taking antidepressants or engaged in psychotherapy will not be excluded. If potential participants are currently prescribed psychotropic medication, they must be on a clinically stable medication regimen for ≥ 6 weeks prior to screening, based on self-report or as verified by medical health records, when available and authorized.
• Participant must be a fluent English speaker.
• Participant must have adequate sensorimotor capacity to perform the program, including visual capacity adequate to read from a computer screen at a normal viewing distance, auditory capacity adequate to understand normal speech, and motor capacity adequate to control and use a mobile device and/or computer as required to complete study activities.
• Participant must have access to wireless Internet connectivity.
• Participant must be willing to communicate with study staff via email.
Exclusion Criteria:
• Participant with unstable and/or untreated conditions that may affect cognition, including untreated substance abuse/dependence disorders, unmanaged cardiovascular disease, endocrine or neurologic disorder, epilepsy, brain injury, hospitalization within 6-weeks of enrollment, ongoing chemotherapy or other cancer treatment (e.g., radiation) .
• Participant with history or current DSM-5 diagnosis of psychosis, such as schizophrenia, schizoaffective disorder, delusion disorder, psychotic disorder NOS, bipolar disorder, substance abuse (<1 year), and/or mood congruent or mood incongruent psychotic features or disorders.
• Participant has a history or current diagnosis of dementia and/or scores less than a 14 (75%) on the UBACC.
• Participant with active suicidal ideations or behaviors within 2 months of screening.
• Participant that shows signs of intoxication due to current substance abuse (including alcohol and/or illegal drugs) during any in person visit. Such participants will have that visit re-scheduled; participants with this problem occurring more than once may be excluded and dropped at the discretion of the Principal Investigators.
• Participant has problems performing assessments or comprehending or following spoken instructions, or those with behaviors during screening or baseline visits that, in the judgment of the screening staff, are likely to present significant problems for the staff conducting assessments.
• Participant is enrolled in a concurrent clinical trial involving an investigational pharmaceutical, nutraceutical, medical device, or behavioral treatment that could affect the outcome of this study. However, participation in standard treatments (e.g., occupational therapy) or use of prescribed medications (e.g., anti-depressants) is allowable..
• Participant is using computer-based cognitive training programs or has used it within a month of the consent date.
Other: Mobile-device, plasticity-based adaptive cognitive treatment
Major Depressive Disorder
Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
This study is designed for the following purpose: - To assess the risk of delayed adverse events (AEs) following exposure to genemodified(GM) T cells - To monitor for long-term persistence of GM T cells, including analysis of vector integration sites, as appropriate. - To monitor for generation of replication competent retroviruses (RCR) - To assess long-term efficacy following treatment with GM T cells - Describe growth, developmental outcome, and sexual maturity status for subjects who were aged < 18 years at time of GM T cell treatment - To assess long term health-related quality of life following treatment with GM T cells
Veronika Bachanova, MD
All
Not specified
Phase 2/Phase 3
NCT03435796
STUDY00006610
Inclusion Criteria:
• Received at least one gene-modified (GM) T-cell infusion in a previous Celgene sponsored or Celgene alliance partner-sponsored study, and have discontinued, or completed the post-treatment follow-up period in the parent treatment protocol, as applicable.
• Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form prior to any study-related assessments/procedures being conducted.
Exclusion Criteria:
Not Applicable
Other protocol-defined inclusion/exclusion criteria apply
Genetic: Gene-modified (GM) T cell therapy
Neoplasms
Long-term follow up, Gene-Modified T Cells, CAR T Cell
Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 1 (MINUTES)
All
18 Years to 60 Years old
N/A
NCT03896425
Inclusion Criteria:
• Ability to provide consent and comply with study procedures.
• Age 18 - 60 years old.
• Estimated IQ range within the range: 70 ≤ IQ ≤ 115.
• No Serious and Persistent Mental Illness (SPMI) or addictive disorder diagnosis as measured by the MINI (Mini International Neuropsychiatric Interview), or sleep disorder;
• Ability to participate in three weekly 45' training sessions over 12 weeks and participate in four assessments.
Exclusion Criteria:
• Any medical condition or treatment with neurological sequelae (e.g. stroke, tumor, loss of consciousness > 30 min, HIV).
• Contraindications for tDCS or MRI scanning (tDCS contraindication: history of seizures; MRI contraindications: The research team will utilize the CMRR Center's screening tools and adhere to the screening SOP during enrollment of all research participants in this protocol. The CMRR Center's screening tools and SOP are IRB approved under the CMRR Center Grant (HSC# 1406M51205) and information regarding screening procedures is publicly available on the CMRR website (CMRR Policies / Procedures).
Device: Transcranial direct current stimulation (tDCS)
Transcranial Direct Current Stimulation, Healthy
tDCS, cognitive training, functional connectivity, non-invasive brain stimulation
Increased thalamocortical connectivity in tdcs-potentiated generalization of cognitive training (MINUTES)
The overarching goals of this proposal are to deploy neuroimaging and cognitive testing to understand how tDCS with cognitive training affect thalamocortical circuitry in individuals with and without psychosis and to examine variability in response within both groups.
Kelvin Lim
All
18 Years to 60 Years old
N/A
NCT03896438
STUDY00003506
Inclusion Criteria:
• Ability to provide consent and comply with study procedures.
• Age 18 - 60 years old.
• Estimated IQ range within the range: 70 ≤ IQ ≤ 115.
• Schizophrenia or schizoaffective disorder as assessed by the MINI (Mini International Neuropsychiatric Interview)(Sheehan et al., 1998).
• Not having a current addictive disorder as measured by MINI (Mini International Neuropsychiatric Interview), or a sleep disorder.
• Ability to participate in three weekly 45' training sessions over 12 weeks and participate in four assessments.
• Clinically stable and on stable medications for at least one month before start of study.
Exclusion Criteria:
• Any medical condition or treatment with neurological sequelae (e.g. stroke, tumor, loss of consciousness > 30 min, HIV).
• Contraindications for tDCS or MRI scanning (tDCS contraindication: history of seizures; MRI contraindications: The research team will utilize the CMRR Center's screening tools and adhere to the screening SOP during enrollment of all research participants in this protocol. The CMRR Center's screening tools and SOP are IRB approved under the CMRR Center Grant (HSC# 1406M51205) and information regarding screening procedures is publicly available on the CMRR website (CMRR Policies / Procedures).
Device: Transcranial Direct Current Stimulation (tDCS)
Transcranial Direct Current Stimulation, Schizophrenia, Schizoaffective Disorder
tDCS, cognitive training, functional connectivity
Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes (SODAS)
All
35 Years and over
N/A
NCT03944616
Inclusion criteria: We will include men, women and non-binary participants with T2D, age 35
years and older, able to provide informed consent, otherwise healthy, who meet the
following criteria:
• Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
• HbA1c 6.5-8.5% at participant screening
• Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
• Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as > 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
• No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
• Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
• Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).
• Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
• "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
• Diabetic Ketoacidosis hospitalization within last 6 months
• Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
• Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
• History of intolerance or allergy to diet beverages or AS or phenylketonuria
• Any condition that is known to affect the validity of the glycemic measures (Hba1c)
• Major cardiovascular disease event or surgery within past 6 months
• Gastrointestinal disease
• Renal or liver disease
• Current treatment for cancer
• Those with major surgery planned or history of bariatric surgery
• Antibiotic treatment (> 6 days) within past 6 months
• Currently pregnant (via self-report) or planning to become pregnant during study period; <1 year postpartum and breast feeding
• Current participation in another interventional clinical trial
• Previous randomization in this study,
• Heavy alcohol consumption (on average >2 drinks/day for women and >3 drinks/day for men)
• Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
• Does not drink diet beverages
• BMI < 20.0 kg/m2
• Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
• HbA1c 6.5-8.5% at participant screening
• Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
• Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as > 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
• No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
• Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
• Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).
Exclusion Criteria:
• Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
• "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
• Diabetic Ketoacidosis hospitalization within last 6 months
• Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
• Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
• History of intolerance or allergy to diet beverages or AS or phenylketonuria
• Any condition that is known to affect the validity of the glycemic measures (Hba1c)
• Major cardiovascular disease event or surgery within past 6 months
• Gastrointestinal disease
• Renal or liver disease
• Current treatment for cancer
• Those with major surgery planned or history of bariatric surgery
• Antibiotic treatment (> 6 days) within past 6 months
• Currently pregnant (via self-report) or planning to become pregnant during study period; <1 year postpartum and breast feeding
• Current participation in another interventional clinical trial
• Previous randomization in this study,
• Heavy alcohol consumption (on average >2 drinks/day for women and >3 drinks/day for men)
• Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
• Does not drink diet beverages
• BMI < 20.0 kg/m2
Behavioral: Diet Beverage, Behavioral: Water
Type 2 Diabetes
Diet beverages, diet, diabetes control, artificial sweeteners, continuous glucose monitor, gut microbiome, metabolomics
Low sulfur fecal transplant for ulcerative colitis
This study is a pilot randomized controlled clinical trial examining how fecal microbiota transplant (FMT) given by capsules can change the bacteria and inflammation in people with active ulcerative colitis (UC). We will look at global changes of bacterial composition while on FMT versus those not on FMT. We are examining some specific groups of bacteria that are related to sulfate reduction. Will will measure the changes of sulfate reducing bacteria over time and among those who get better and those who don't. Overall, we aim to determine if we can alter the microbiota in UC towards a healthy, more diverse microbiota resembling the donor using capsule FMT material.
Byron Vaughn
All
18 Years to 89 Years old
Phase 1
NCT03948919
STUDY00005279
Inclusion Criteria:
• Able and willing to provide consent
• English speaking
• Diagnosis of ulcerative colitis based on typical clinical-histopathic diagnosis
• Diagnosis of ulcerative colitis > 3 months
• Active disease on endoscopy (endoscopic Mayo subscore ≥ 1)
• Evidence of inflammation extending beyond a minimum of 20cm
• Any ongoing ulcerative colitis therapy must be at stable doses for 4 weeks prior to study and remain stable over the course of the study
Exclusion Criteria:
• Extensive bowel resection
• Presence of ileostomy or colostomy
• Suspicion of ischemic colitis, radiation colitis or microscopic colitis
• Diagnosis of Crohn's disease
• Diagnosis of per-anal fistula or abscess
• Adenomatous polyps that have not been removed
• Use of pre or probiotics within 30 days of randomization
• Pregnancy
• Severe food allergies
• End stage liver disease or cirrhosis
• An absolute neutrophil count < 500 cell/µL
• Life expectancy < 6 months
Drug: Fecal microbiota, Other: Placebo
Ulcerative Colitis, Digestive & Liver Health
inflammatory bowel disease
MT2021-03: A Multicenter Randomized Controlled Trial of Best Available Therapy versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (BEAT-MS)
Adam Carpenter
All
18 Years to 55 Years old
Phase 3
NCT04047628
STUDY00007288
Inclusion Criteria:
Participant(s) must meet all of the following criteria to be eligible for this study:
• Diagnosis of Multiple Sclerosis (MS) according to the 2017 McDonald Criteria
• (Kurtzke) Expanded Disability Status Scale (EDSS) ≥ 2.0 and ≤ 5.5 at the time of randomization (Day 0)
• T2 abnormalities on brain Magnetic Resonance Imaging (MRI) that fulfill the 2017 McDonald MRI criteria for dissemination in space --A detailed MRI report or MRI images must be available for review by the site neurology investigator.
• Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of treatment failure in the 36 months prior to the screening visit (Visit -2). The two treatment failure events need not occur during treatment with different Disease- modifying Therapy (DMT), but must meet all the criteria as described below:
• Each episode of treatment failure must occur following ≥ 3 months of treatment with an FDA-approved DMT for relapsing forms of MS, or with rituximab or ofatumumab, and
• At least one episode of treatment failure must occur with an oral agent or a monoclonal antibody, specifically: dimethyl fumarate (Tecfidera®), diroximel fumarate, teriflunomide (Aubagio®), cladribine (Mavenclad®), daclizumab (Zinbryta®), siponimod (Mayzent®), ozanimod, fingolimod (Gilenya®), rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), or ofatumumab (Arzerra®), and
• At least one episode of treatment failure must have occurred within the 12 months prior to the screening visit (Visit -2), and
• At least one episode of treatment failure must be a clinical MS relapse (see item d.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item d.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee, and ii. MRI evidence of disease activity must include ≥ 2 unique active lesions on a brain or spinal cord MRI. A detailed MRI report or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following:
• A gadolinium-enhancing lesion, or
• A new non-enhancing T2 lesion compared to a reference scan obtained not more than 24 months prior to the screening visit (Visit -2).
• Candidacy for treatment with at least one of the following high efficacy DMTs: Cladribine, natalizumab, alemtuzumab, ocrelizumab, rituximab, and ofatumumab (after approval by the FDA for relapsing MS). --Note: Rituximab, ofatumumab, and ocrelizumab are considered equivalent for candidacy. Candidacy for treatment for each DMT is defined as meeting all of the following:
• No prior treatment failure with the candidate DMT, and
• No contraindication to the candidate DMT, and
• No treatment with the candidate DMT in the 12 months prior to screening.
• Insurance or public funding approval for MS treatment with at least one candidate DMT, and
• Ability to comply with study procedures and provide informed consent, in the opinion of the investigator.
Exclusion Criteria:
Subject(s) who meet any of the following criteria will not be eligible for this study:
• Diagnosis of primary progressive Multiple Sclerosis (MS) according to the 2017 McDonald criteria
• History of neuromyelitis optica or anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies associated encephalomyelitis
• Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer
• Either of the following within one month prior to randomization (Day 0):
• Onset of acute MS relapse, or
• Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
• Initiation of natalizumab, alemtuzumab, ocrelizumab, or rituximab between screening visit (Visit -2) and randomization (Day 0)
• Brain MRI or Cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML)
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)
• Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis
• History of sickle cell anemia or other hemoglobinopathy
• Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C -Note: Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Presence or history of mild to severe cirrhosis
• Hepatic disease with the presence of either of the following:
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin
• 3.0 times the ULN in the presence of Gilbert's syndrome, or
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
• Evidence of HIV infection
• Positive QuantiFERON - TB Gold or TB Gold Plus test results (e.g., blood test results that detect infection with Mycobacterium tuberculosis) Note: A Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON - TB Gold or TB Gold Plus test.
• Active viral, bacterial, endoparasitic, or opportunistic infections
• Active invasive fungal infection
• Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist
• Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0)
• Presence or history of clinically significant cardiac disease including:
• Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions
• Coronary artery disease with a documented diagnosis of either:
• Chronic exertional angina, or
• Signs or symptoms of congestive heart failure.
• Evidence of heart valve disease, including any of the following:
• Moderate to severe valve stenosis or insufficiency,
• Symptomatic mitral valve prolapse, or
• Presence of prosthetic mitral or aortic valve.
• Left ventricular ejection fraction (LVEF) < 50%
• Impaired renal function defined as Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Forced expiratory volume in one second (FEV1) <70% predicted (no bronchodilator)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) < 70% predicted
• Poorly controlled diabetes mellitus, defined as HbA1c >8%
• History of malignancy, with the exception of adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. -Note:Malignancies for which the participant is judged to be cured by therapy completed at least 5 years prior to randomization (Day 0) will be considered on an individual basis by the study adjudication committee.
• Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following:
• systemic lupus erythematous
• systemic sclerosis
• rheumatoid arthritis
• Sjögren's syndrome
• polymyositis
• dermatomyositis
• mixed connective tissue disease
• polymyalgia rheumatica
• polychondritis
• sarcoidosis
• vasculitis syndromes, or
• unspecified collagen vascular disease.
• Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer
• Prior history of AHSCT
• Prior history of solid organ transplantation
• Positive pregnancy test or breast-feeding
• Inability or unwillingness to use effective means of birth control
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
• Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent
• History of hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with gadolinium administration
• Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
• Presence or history of other neurological disorders, including but not limited to:
• central nervous system (CNS) or spinal cord tumor
• metabolic or infectious cause of myelopathy
• genetically-inherited progressive CNS disorder
• CNS sarcoidosis, or
• systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
• Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality, or
• Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
Procedure: Autologous Hematopoietic Stem Cell Transplantation, Biological: Best Available Therapy (BAT)
Rare Diseases, Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT, Clinics and Surgery Center (CSC)
The role of cytomegalovirus and inflammation on patient symptoms and outcomes in ovarian cancer
The central research idea for this award is that CMV reactivation is an unrecognized complicating factor in the treatment of ovarian cancer. Based on preliminary data, our hypotheses are: a) ovarian cancer patients with elevated biomarkers of CMV report greater fatigue and poorer quality of life; b) CMV and inflammation (C-reactive protein; CRP) levels in ovarian cancer patients are higher post-chemotherapy than baseline; c) ovarian cancer patients who experience increases in CMV and/or CRP report greater fatigue and poorer quality of life; d) ovarian cancer patients who experience increases in CMV and CRP will have shorter recurrence-free and overall survival. We propose the following specific aims and studies to address these research questions: Aim 1: Determine the relationship between CMV and ovarian cancer patient-reported symptoms post-treatment. A cross-sectional study of 200 women with ovarian cancer within two years of completing first line chemotherapy will be recruited for a one-time blood draw and survey. We will assess CMV status by measuring IgG serology and CMV DNA levels in serum (indicative of active infection/reactivation) and determine their relationship with patient-reported symptoms including fatigue and quality of life. Aim 2: Characterize the changes in CMV and CRP levels following chemotherapy and their association with patient symptoms and outcomes. A prospective study of 150 women with newly diagnosed ovarian cancer will evaluate the association between serum CMV IgG, CRP IgG, and CMV DNA levels and patient-reported symptoms, recurrence-free and overall survival. Planned blood samples include before, after and 6 months post-chemotherapy completion with planned surveys and clinical follow-up at least every six months for five years.
Rachel Vogel
Female
18 Years and over
NA
NCT03921658
STUDY00005451
Inclusion Criteria:
• Age ≥18
• Ability to read and write in English
• women with newly diagnosed with ovarian, primary peritoneal, or fallopian tube cancer
• Treatment plan includes chemotherapy
• Able to provide written voluntary consent before performance of any study related procedure.
• Cohort 1 only: within 2 years of completing initial chemotherapy treatment
• Cohort 2 only: prior to starting chemotherapy
Exclusion Criteria:
• Inability to provide informed written consent
• Previous exposure to chemotherapy
• Life expectancy < 3 months or in hospice care or nursing home
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
Clinics and Surgery Center (CSC)
Algorithms for programming DBS systems for ET
This study seeks to leverage subject-specific computational models that can predict neural activation of axonal pathways adjacent to the active electrode(s) and implicated in the therapeutic mechanisms of Vim-DBS to in turn guide clinicians with which stimulation settings are likely to be the most therapeutic on tremorous activity.
Matthew Johnson
All
21 Years and over
N/A
NCT03984643
STUDY00005218
Inclusion Criteria:
• diagnosis of ET
• medication-refractory tremor
• VIM-DBS implant (unilateral or bilateral)
• 7T MRI pre-operative scan under Dr. Harel's IRB (institutional review board) protocol (#1210M22183)
• Post-operative CT scan
Exclusion Criteria:
• history of musculoskeletal disorders that affect movement of the limbs
• other significant neurological disorder
• prior history of stereotactic neurosurgery (other than VIM-DBS surgery)
• pregnancy
Device: Vim-Deep Brain Stimulation
Essential Tremor
Clinics and Surgery Center (CSC)
Hemodynamic-GUIDEd Management of Heart Failure (GUIDE-HF) (GUIDE-HF)
This clinical trial is intended to demonstrate the effectiveness of the CardioMEMS™ HF System in patients with New York Heart Association (NYHA) Class II, III, or IV Heart Failure (HF) who have an elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or an elevated Brain Natriuretic Peptide (BNP)) and/or a prior HF Hospitalization (HFH).
Tamas Alexy
All
18 Years and over
N/A
NCT03387813
STUDY00006017
Inclusion Criteria:
• Diagnosis and treatment for heart failure (HF) (regardless of left ventricular ejection fraction (LVEF)) for > 90 days prior to the date of consent: a. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United States, with any intolerance documented.
• GUIDE-HF Randomized Arm Only: NYHA Class II, III or IV HF symptoms documented within 30 days prior to consent.
• GUIDE-HF Single Arm Only: NYHA Class III HF symptoms documented within 30 days prior to consent.
• HF hospitalization (HFH) within 12 months prior to consent and/or elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or Brain Natriuretic Peptide (BNP)) within 30 days prior to consent defined as:
• Subjects with LVEF ≤ 40%: NT-proBNP ≥ 1000 pg/mL (or BNP ≥ 250 pg/mL).
• Subjects with LVEF > 40%: NT-proBNP ≥ 700 pg/mL (or BNP ≥ 175 pg/mL).
• Thresholds for NT-proBNP and BNP (for both LVEF ≤ 40% and LVEF > 40%) will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2
• ≥ 18 years of age
• Chest circumference of < 65 inches, if BMI is > 35 kg/m2
• Written informed consent obtained from subject
• Willing and able to upload pulmonary artery (PA) pressure information and comply with the follow-up requirements
Exclusion Criteria:
• Intolerance to all neuro-hormonal antagonists (i.e., intolerance to angiotensin converting enzyme-inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin-neprilysin inhibitors (ARNi), hydralazine/isosorbide dinitrate and beta-blockers)
• ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes)
• Received or are likely to receive an advanced therapy (e.g., mechanical circulatory support or cardiac transplant) in the next 12 months
• NYHA Class IV HF patients with:
• Continuous or chronic use of scheduled intermittent inotropic therapy for HF and an INTERMACS level of ≤ 4, OR
• Persistence of fluid overload with maximum (or dose equivalent) diuretic intervention
• Glomerular Filtration Rate (eGFR) < 25 mL/min and non-responsive to diuretic therapy, or receiving chronic dialysis
• Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy for one month post-implantation
• Significant congenital heart disease that has not been repaired and would prevent implantation of the CardioMEMS™ PA Sensor
• Implanted with mechanical right heart valve(s)
• Unrepaired severe valvular disease
• Pregnant or planning to become pregnant in the next 12 months
• An active, ongoing infection, defined as being febrile, an elevated white blood cell count, on intravenous antibiotics, and/or positive cultures (blood, sputum or urine).
• History of current or recurrent (≥ 2 episodes within 5 years prior to consent) pulmonary emboli and/or deep vein thrombosis
• Major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke, etc.) within 90 days prior to consent
• Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to consent
• Enrollment into another trial with an active treatment arm
• Anticipated life expectancy of < 12 months
• Any condition that, in the opinion of the Investigator, would not allow for utilization of the CardioMEMS™ HF System to manage the subject using information gained from hemodynamic measurements to adjust medications, including the presence of unexpectedly severe pulmonary hypertension (e.g., trans-pulmonary gradient >15) at implant right heart catheterization (RHC), a history of non-compliance, or any condition that would preclude CardioMEMS™ PA Sensor implantation
Device: CardioMEMS™ HF System
Heart Failure, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure，Congestive, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction, Heart Failure, With Decompensation
Heart Failure, Hemodynamic Monitoring, CardioMEMS, Pulmonary Artery Pressure, Clinics and Surgery Center (CSC)
Phase 1/2 Study to Evaluate Palbociclib (IBRANCE?) in Combination With Irinotecan and Temozolomide or in Combination with Topotecan and Cyclophosphamide in Pediatric Patients With Recurrent or Refractory Solid Tumors Protocol No.: ADVL1921/A5481092
This is a Phase 1/2 multicenter, open-label study to evaluate palbociclib in combination with either irinotecan (IRN) and temozolomide (TMZ) or topotecan (TOPO) and cyclophosphamide (CTX) chemotherapy in children, adolescents and young adults with recurrent or refractory solid tumors. The study consists of a non- randomized Phase 1 portion for recurrent or refractory solid tumors followed by potential non- randomized tumor specific cohort(s) and a randomized, Phase 2 portion for recurrent or refractory EWS.
Emily Greengard
All
2 Years to 20 Years old
Phase 2
NCT03709680
STUDY00007068
Inclusion:
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma. Histopathology confirmation of EWSR1-ETS or FUS-ETS rearrangement is required or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or refractory disease with no known bone marrow metastases and at least evaluable disease.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
• Evidence of a personally signed and dated informed consent document indicating that the patient or a legally acceptable representative/parent(s)/legal guardian of minors, has been informed of all pertinent aspects of the study. Minor study patients also must provide age appropriate assent according to the local guidelines, where applicable.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 :prior treatment with a CDK4/6 inhibitor or prior treatment with an IRN and/or TMZ-containing regimen.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Prior growth factors (including filgrastim) within 7 days before study entry or PEG-filgrastim within 14 days before study entry.
• Radiation therapy within 14 days before study entry.
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Previous high dose chemotherapy requiring stem cell rescue within 90 days or persistent AE >Grade 1.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.Phase 2 portion patients with bone marrow involvement are excluded.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
• Other severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 after the last dose of investigational product.
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma. Histopathology confirmation of EWSR1-ETS or FUS-ETS rearrangement is required or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or refractory disease with no known bone marrow metastases and at least evaluable disease.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
• Evidence of a personally signed and dated informed consent document indicating that the patient or a legally acceptable representative/parent(s)/legal guardian of minors, has been informed of all pertinent aspects of the study. Minor study patients also must provide age appropriate assent according to the local guidelines, where applicable.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 :prior treatment with a CDK4/6 inhibitor or prior treatment with an IRN and/or TMZ-containing regimen.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Prior growth factors (including filgrastim) within 7 days before study entry or PEG-filgrastim within 14 days before study entry.
• Radiation therapy within 14 days before study entry.
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Previous high dose chemotherapy requiring stem cell rescue within 90 days or persistent AE >Grade 1.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.Phase 2 portion patients with bone marrow involvement are excluded.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
• Other severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 after the last dose of investigational product.
Drug: Palbociclib, Drug: Temozolomide, Drug: Irinotecan, Drug: Topotecan, Drug: Cyclophosphamide
Ewing Sarcoma, Solid Tumors, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), neuroblastoma (NBL), Brain tumor
Dried Blood Spot Testing of CMV Detection in HCT Recipients
Subject-Collected Dried Blood Spot CMV Testing to Optimize Preemptive Therapy Late After Allogeneic HCT
Jo-Anne Young, MD
All
15 Years to 99 Years old
N/A
NCT03910478
STUDY00005408
Inclusion Criteria:
Randomized Cohort:
• Must be >/= 15 years of age at the time of enrollment
• Must be able to provide written consent and complete the informed consent
• Must have received allogeneic hematopoietic cell transplantation within 60-180 days prior to randomization
• Cytomegalovirus (CMV) seropositive or had a donor who was CMV positive
• One or both of the following:
• CMV event* within the first 100 days post-transplant requiring anti-viral treatment
• Receipt of CMV prophylaxis**(for at least 30 days) prior to randomization. Continuation of letermovir prophylaxis after day 100 per institutional standard of care is permitted * CMV event defined as deoxyribonucleic acid (DNA) detection or disease ** Anti-viral treatment or prophylaxis includes ganciclovir, valganciclovir, foscarnet, or letermovir
• Direct availability to the internet either by a computer in the residence or a smart phone
• Had at least one or more of these conditions:
• HLA mismatch*
• umbilical cord blood source**
• Graft versus host disease (GVHD)***
• T-cell depletion**** * Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B, or -DR, Haploidentical donor, Unrelated donor with at least one mismatch at one of the following four HLA-gene loci: HLA-A, -B, -C and -DRB1
• Use of umbilical cord blood as stem cell source ***Acute or chronic GVHD requiring topical steroid for gastrointestinal (GI) GVHD and/or systemic steroid treatment (>/= 1 mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 6 weeks prior to enrollment
• Subjects who have received partial or full T-cell depletion (with or without GVHD). T-cell depletion can be given as either ex-vivo or in-vivo for GVHD prophylaxis. T-cell depleting agents include, but are not limited to, anti-thymocyte globulin (ATG) and alemtuzumab Observation Cohort:
• Must be >/= 15 years of age at the time of enrollment
• Must have one of the following:
• Consented for retrospective studies at their transplant center, or
• Be included under the auspices of the site's IRB approved waiver of additional consent for retrospective studies
• Must have received allogeneic hematopoietic cell transplantation within 360 days prior to enrollment
• CMV seropositive or had a donor who was CMV positive
• One or both of the following:
• CMV event* within the first 100 days post-transplant requiring anti-viral treatment
• Receipt of CMV prophylaxis**(for at least 30 days) prior to registration. Continuation of letermovir prophylaxis after day 100 per institutional standard of care is permitted * CMV event defined as DNA detection or disease ** Anti-viral treatment or prophylaxis includes ganciclovir, valganciclovir, foscarnet, or letermovir
• Meet at least one or more of criteria of the following:
• HLA mismatch*
• umbilical cord blood source**
• GVHD***
• T-cell depletion****
• Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B, or -DR, Haploidentical donor, Unrelated donor with at least one mismatch at one of the following four HLA-gene loci: HLA-A, -B, -C and -DRB1 **Use of umbilical cord blood as stem cell source ***Acute or chronic GVHD requiring topical steroid for GI GVHD and/or systemic steroid treatment (>/= 1 mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 6 weeks prior to enrollment ****Subjects who have received partial or full T-cell depletion (with or without GVHD). T-cell depletion can be given as either ex-vivo or in-vivo for GVHD prophylaxis. T-cell depleting agents include, but are not limited to, anti-thymocyte globulin (ATG) and alemtuzumab
Exclusion Criteria:
Randomized Cohort:
• Inability to fully comprehend the study website and study procedures
• Any other condition, which in the opinion of the investigator would interfere with successful completion of this clinical trial
• Morphological relapse (bone marrow or peripheral blood blast) prior to registration Observational Cohort:
• Did not meet all inclusion criteria
• Morphological relapse (bone marrow or peripheral blood blast) prior to registration
Device: DBS Self-Collection Kit, Other: Standard Control Strategy
Cytomegalovirus Infection
Allogeneic, Cytomegalovirus, Dried Blood Spot, Hematopoietic cell transplantation
HEM-POWR: Observational Study Evaluating Effectiveness and Safety of Real-World Treatment with Damoctocog alfa pegol in Previously Treated Patients with Hemophilia A (HEM-POWR)
Multinational, open-label, prospective, non-interventional, multicenter, cohort study. The objectives of this study are to assess the effectiveness and long term safety of prophylaxis with damoctocog alfa pegol in the real-world setting through the collection of total bleeding events and analysis of the annualized bleeding rate (ABR) in the different prophylaxis regimens (following approved local label or any other regimen prescribed by the physician as part of normal clinical practice) in patients with hemophilia A. The analyses will be stratified, based on severity of hemophilia, severity of patient bleeding profile, disease characteristics, prophylaxis regimen, age, and time on treatment (i.e., damoctocog alfa pegol-naive or not).
Joan Beckman
All
Not specified
Post Market Monitoring
NCT03932201
STUDY00006977
Inclusion Criteria:
• Diagnosis of hemophilia A.
• Patients previously treated for Hemophilia A.
• Patients without previous history of inhibitors or patients with previous history of inhibitors on standard prophylaxis therapy for at least 1 year prior to study entry.
• No current evidence of FVIII inhibitor or clinical suspicion of FVIII inhibitor.
• Initiation of or currently on damoctocog alfa pegol with any kind of treatment modality (on-demand, prophylaxis, or intermittent prophylaxis).
• Signed informed consent/assent.
Exclusion Criteria:
• Concurrent participation in an investigational program with interventions outside of routine clinical practice.
• Diagnosis of any other bleeding/coagulation disorder other than hemophilia A.
• Contra-indications according to the local marketing authorization.
• Patient on immune tolerance induction (ITI) treatment at the time of enrollment.
Drug: Damoctocog alfa pegol (Jivi, Bay94-9027)
Hemophilia A
Pediatric cGVHD Symptom Scale
To develop a psychometrically valid Pediatric cGVHD Symptom Scale (PCSS) and a companion parent-proxy measure as counterparts to the Lee cGVHD Symptom Scale.
Margaret MacMillan, MD
All
5 Years and over
NA
NCT04044365
STUDY00008469
• INCLUSION CRITERIA: Pediatric Subject
Inclusion Criteria:
• Children aged 5 to 17 years old, who have undergone prior allogeneic stem cell transplant
• Clinical diagnosis of cGVHD
• Currently receiving systemic treatment for cGVHD (including phototherapies), or has had systemic therapy for cGVHD tapered to discontinuation within the past 12 months
• No evidence of malignant disease relapse including molecular relapse and minimal residual disease. Patients with mixed chimerism are eligible to participate
• Parent or guardian ability and willingness to sign a written informed consent document
• Subjects must be able to comprehend and speak the English language
• Subjects may participate in both Project 1 and Project 2 of the study. Participation in Project 1 is not required in order to be eligible to participate in Project 2.
• Parent or Guardian Proxy Inclusion Criteria
• Parent or guardian of participating subject
• Must be willing and able to provide informed consent. Parent or guardian (proxy) must be able to comprehend and speak the English language EXCLUSOIN CRITERIA:
• Patients who completed systemic treatment more than 3 months prior to enrollment or are receiving topical therapy only.
• Patients may be excluded from this study if in the judgment of the Principal or Associate Investigator, the subject is too ill, or subject s cognitive ability would compromise their ability to participate in study related procedures.
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Stem Cell Transplant, Phototherapies, Graft Vs Host Disease, Natural History
Using Smartphone Sensor Technology to Characterize Ambulatory Patterns of Participants With Peripheral Artery Disease
Supervised exercise training (SET) improves functioning and quality of life for patients with peripheral artery disease (PAD). However, these programs have primarily been conducted in research settings, thus the physical activity that patients complete in real-world settings (urban and rural hospitals) is unknown. The proposed project will use a novel smartphone app called Daynamica, to summarize patients activity patterns and also to enhance patient-study staff communication and subsequently improve PAD patient health outcomes.
All
40 Years and over
NCT04124315
Inclusion Criteria:
• Diagnosis of atherosclerotic PAD and referred to hospital-based SET
• Ability to complete an evaluation of physical function and walk on a treadmill
• Resting ankle-brachial index (ABI) of ≤0.90 or stenosis ≥50% in a peripheral vessel or those with lifestyle limiting vascular-related claudication
• Those with a resting ABI of 0.91-0.99 (borderline) who have completed an exercise-ABI assessment with a >20% drop compared to resting values
• Those with ABI >1.40 who have had an abnormal toe-brachial index of ≤0.70
Exclusion Criteria:
• Lower extremity amputation(s) which interfere(s) with walking on the treadmill.
• Individuals with critical limb ischemia defined by ischemic rest pain or ischemic ulcers/gangrene on the lower extremities
• PAD of non-atherosclerotic nature (e.g., fibromuscular dysplasia, irradiation, endofibrosis)
• Females who are pregnant
• Coronary artery bypass grafts or major surgical procedures within 6 months prior to screening
• Individuals whose walking exercise is primarily limited by symptoms of chronic obstructive pulmonary disease, angina, or heart failure
• Individuals who have had a myocardial infarction within 3 months prior to screening
• Individuals who have had a transient ischemic attack or stroke 3 months prior to screening
• Individuals with uncontrolled hypertension (≥180 systolic or ≥100 diastolic resting blood pressure) during screening
• Poorly controlled diabetes defined as glycated hemoglobin >12%
• Abnormal results of blood work not conducive to safely participating in an exercise trial (e.g., anemic, electrolyte abnormalities)
• Inability to speak English
• Other clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, hematological, or metabolic disease that is, in the opinion of the study team, not stabilized or may otherwise confound the results of the study
Other: Accelerometry, Other: Daynamica app
Peripheral Artery Disease
peripheral artery disease, accelerometer, smartphone, supervised exercise therapy
Enhanced Spatial Targeting in ECT Utilizing Focally Electrically-administered Seizure Therapy (FEAST)
Twenty ECT eligible TRD patients will receive a course of FEAST with up to 15 sessions (including titration) in an open trial design. Sessions 2,3 and 4 will be cross-randomized between ‘typical’ FEAST electrode configuration, the same electrode placement but a reversed polarity of current flow (RP FEAST) and the reverse electrode configuration FEAST (RC FEAST). Electrophysiological markers of the induced seizure will be captured with a 6-lead EEG placed over bilateral frontal, temporal and parietal lobes.
Ziad Nahas
All
18 Years to 90 Years old
N/A
NCT04099342
STUDY00006734
Inclusion Criteria:
• Diagnosis of major depressive disorder using mini-7 to derive RDC; DSM-IV
• Pretreatment HRSC score greater than or equal to 18
• ECT indicated by physician evaluation
• Willing and capable of providing informed consent as determined by physician evaluation
Exclusion Criteria:
• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder as determined by mini-7; rapid cycling defined as greater than or equal to four episodes in past year
• History of neurological illness or insult other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia) determined by physician evaluation and medical history
• Alcohol or substance abuse or dependence in the past year (RDC) determined by physician evaluation
• Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-IV), pregnancy, or epilepsy determined by physician evaluation
• Requires especially rapid antidepressant response due to suicidality, psychosis, inanition, psychosocial obligations, etc. determined by physician evaluation
• ECT in the past six months determined by physician evaluation and medical history
• Pregnancy as determined by urine pregnancy test and clinical interview
Device: FEAST, Device: FEAST RP, Device: FEAST RC
Treatment Resistant Depression
PRI-VENT FSGS: Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant
PRI-VENT FSGS is a phase III, multicenter, randomized, open label, clinical trial to test the hypothesis that plasmapheresis plus rituximab prior to kidney transplantation can prevent recurrent FSGS in children and adults.
Priya Verghese
All
1 Year to 65 Years old
Phase 3
NCT03763643
STUDY00004388
In order to be eligible to participate in this study, an individual must meet all of the
following criteria:
• Age 1-65 years at the time of kidney transplant
• Biopsy proven diagnosis of primary FSGS or minimal change disease
• History of nephrotic syndrome (proteinuria, edema, hypoalbuminemia)
• First kidney transplant or second or third transplant with a history of recurrent FSGS in the first or second kidney transplant.
• The patient (if ≥18 years old) or the child's parent or guardian must be able and willing to give written informed consent and comply with the requirements of the study protocol. Patient assent if <18 years old will be required per local IRB requirements.
• Negative urine pregnancy test prior to randomization (for females who are post-menarche).
• Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab. An individual who meets any of the following criteria will be excluded from participation in this study:
• Known genetic cause of FSGS 2. Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.) 3. 4. Received rituximab within 1 year prior to transplant 5. Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins 6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 7. Known active bacterial, viral (e.g. HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit.
• Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer) 9. ANC < 1.5 x 103 10. Hemoglobin: < 8.0 gm/dL 11. Platelets: < 100,000/mm 12. AST or ALT >2.5 x Upper Limit of Normal at the local institution's laboratory 13. History of drug, alcohol, or chemical abuse within 6 months prior to screening visit.
• Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential 15. Concomitant malignancies or previous malignancies 16. History of psychiatric disorder that would interfere with normal participation in this protocol 17. History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease) 18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 19. Inability to comply with study and follow-up procedures
• Age 1-65 years at the time of kidney transplant
• Biopsy proven diagnosis of primary FSGS or minimal change disease
• History of nephrotic syndrome (proteinuria, edema, hypoalbuminemia)
• First kidney transplant or second or third transplant with a history of recurrent FSGS in the first or second kidney transplant.
• The patient (if ≥18 years old) or the child's parent or guardian must be able and willing to give written informed consent and comply with the requirements of the study protocol. Patient assent if <18 years old will be required per local IRB requirements.
• Negative urine pregnancy test prior to randomization (for females who are post-menarche).
• Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab. An individual who meets any of the following criteria will be excluded from participation in this study:
• Known genetic cause of FSGS 2. Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.) 3. 4. Received rituximab within 1 year prior to transplant 5. Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins 6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 7. Known active bacterial, viral (e.g. HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit.
• Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer) 9. ANC < 1.5 x 103 10. Hemoglobin: < 8.0 gm/dL 11. Platelets: < 100,000/mm 12. AST or ALT >2.5 x Upper Limit of Normal at the local institution's laboratory 13. History of drug, alcohol, or chemical abuse within 6 months prior to screening visit.
• Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential 15. Concomitant malignancies or previous malignancies 16. History of psychiatric disorder that would interfere with normal participation in this protocol 17. History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease) 18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 19. Inability to comply with study and follow-up procedures
Drug: Rituximab, Procedure: Plasmapheresis
Focal Segmental Glomerulosclerosis
Clinics and Surgery Center (CSC)
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients (365 Days to 31 Years) with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better then combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Peter Gordon
All
365 Days to 31 Years old
Phase 3
NCT03914625
STUDY00007530
Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days 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.
Exclusion Criteria:
• Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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.
Drug: Asparaginase Erwinia chrysanthemi, Biological: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Down Syndrome
A Phase II Study of Carboplatin, Cabazitaxel and Abiraterone in High Volume Metastatic Castration Sensitive Prostate Cancer (CASCARA)
This is a phase II clinical trial in participants with metastatic castration sensitive prostate cancer who are still responding to hormone therapy (androgen deprivation therapy or ADT). This study is done to see if giving a course of anti-cancer drugs, carboplatin and cabazitaxel, followed by an oral drug, abiraterone, improves cancer control as measured by prostate-specific antigen (PSA) level (may indicate the presence of prostate cancer) and imaging studies (e.g. CT scan, bone scan).
Emmanuel Antonarakis
Male
18 Years and over
Phase 2
NCT03934840
STUDY00006089
Inclusion Criteria:
• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
• Histologically confirmed prostate cancer.
• High volume metastatic disease (defined as the presence of visceral metastases or ≥3 bone lesions).
• ADT for ≤3 months by day 1 of study chemotherapy; Prior episodes of ADT are allowed (i.e. ADT used previously in courses of radiation).
• Testosterone <50 ng/dL. Patients must continue primary ADT with an LHRH analogue if they have not undergone orchiectomy.
• ECOG Performance Status 0 or 1 (see Appendix A)
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 × 10^9/L
• Platelets ≥ 100 × 10^9/L
• Hemoglobin ≥ 9 g/dl
• Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min
• In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and AST <5 x ULN
• Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
• Sexually active males must use a condom during intercourse while taking study drugs and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Fertile males must use a condom with spermicide (double barrier method).
• Age ≥ 18 years
Exclusion Criteria:
• Prior exposure to any chemotherapy, PARPi, or immunotherapy for prostate cancer.
• Prior abiraterone or enzalutamide, unless therapy was for < 2 weeks
• Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose.
• Other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of chemotherapy (with the exception of anti-androgens like bicalutamide).
• PSA <2.0 ng/mL at diagnosis.
• If present, peripheral neuropathy must be ≤ Grade 1
• Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) prior to starting the study treatment
• Clinically stable CNS tumor at the time of screening.
• Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement
• Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of treating investigator.
• Patient has a history of non-compliance to medical regimen or inability to grant consent.
Drug: Cabazitaxel, Drug: Carboplatin, Drug: Abiraterone, Drug: Prednisone
Prostate Cancer
Clinics and Surgery Center (CSC)
COG ADVL1823 - Larotrectinib (LOXO-101, NSC# 788607, IND# 141824) for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias
This is a non-randomized, open label, phase II trial that will study the side effects and how well larotrectinib works in treating patients (≤ 30 years of age) with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that has come back. Larotrectinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Emily Greengard
All
up to 30 Years old
Phase 2
NCT03834961
STUDY00007876
Inclusion Criteria:
• COHORT A: Patients must have a histologic diagnosis of infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified in a Clinical Laboratory Improvement Act/College of American Pathologists (CLIA/CAP) certified laboratory. Fusions may be identified by fluorescence in situ hybridization (FISH) or molecular techniques (reverse transcriptase-polymerase chain reaction [RT-PCR] using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, an ETV6 rearrangement is sufficient for eligibility in Cohort A. Identification of the upstream TRK fusion partner is not required.
• COHORT B: Patients must have a histologic diagnosis of any solid tumor other than infantile fibrosarcoma, including central nervous system (CNS) tumors but excluding high grade gliomas. An NTRK1, NTRK2, or NTRK3 fusion must be identified in a CLIA/CAP certified laboratory. Fusions may be identified by FISH or molecular techniques (RT-PCR using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, there must be an identified rearrangement in NTRK1, NTRK2, or NTRK3 (e.g., an ETV6 rearrangement is not sufficient for eligibility) unless the patient has a diagnosis of congenital mesoblastic nephroma in which case an ETV6 rearrangement is sufficient for eligibility. Identification of the upstream TRK fusion partner is not required.
• COHORT C: Patients must have a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified in a CLIA/CAP certified laboratory. Fusions may be identified by FISH or molecular techniques (RT-PCR using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, there must be an identified rearrangement in NTRK1, NTRK2, or NTRK3 (e.g., an ETV6 rearrangement is not sufficient for eligibility). Identification of the upstream TRK fusion partner is not required.
• SOLID TUMORS (COHORTS A AND B): Patients must have measurable disease. Patients must have disease that cannot be completely resected without a predicted functional, neurologic, or significant cosmetic deficit in the opinion of the investigator.
• LEUKEMIA (COHORT C): Patients must have >= 5% blasts in the bone marrow. Extramedullary disease is permitted.
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. NOTE: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• COHORTS A AND B: No prior anti-cancer therapy, including radiotherapy, other than surgical resection is permitted.
• Patients who experience recurrence after surgery alone and no other anti-cancer therapy will be eligible.
• If not eligible due to prior anticancer therapy, patients may be eligible for the larotrectinib arm of Pediatric MATCH (APEC1621A) or treatment with commercial larotrectinib off study.
• COHORT C: Patients with relapsed leukemia (Cohort C) must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately.
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
• A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine [6MP], and/or methotrexate).
• A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
• >= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
• Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last dose of agent. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
• Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator.
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors )
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD).
• Autologous stem cell infusion including boost infusion: >= 42 days.
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial BM radiation.
• Radiopharmaceutical therapy (e.g., radiolabeled antibody): >= 42 days after systemically administered radiopharmaceutical therapy.
• Patients must not have received prior exposure to TRK inhibitors (including larotrectinib, LOXO-195, entrectinib, lorlatinib, crizotinib, or lestaurtinib).
• For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: Hemoglobin >=
• 0 g/dL at baseline (may receive red blood cell [RBC] transfusions).
• Patients with solid tumors with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity.
• For patients with leukemia: Platelet count >= 20,000/mm^3 (within 7 days prior to enrollment) (may receive platelet transfusions; must not be known to be refractory to red cell or platelet transfusion)
• For patients with leukemia: Hemoglobin >= 8.0 g/dL at baseline (within 7 days prior to enrollment) (may receive RBC transfusions; must not be known to be refractory to red cell or platelet transfusion)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
• 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
• 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
• 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
• 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
• 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
• 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
• >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL)
• For patients < 1 month of age, serum creatinine levels must be < 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients < 1 month of age or the creatinine clearance or radioisotope GFR must be >= 70 mL/min/1.73 m^2.
• Patients with solid tumors: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment). After approval of the study chair or designee, infants with a higher total bilirubin due to physiologic or breast milk jaundice are eligible if the conjugated (direct) bilirubin is =< 2 mg/dL
• Patients with solid tumors: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Patients with solid tumors: Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
• Patients with leukemias: Conjugated (direct) bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
• Patients with leukemias: SGPT (ALT) =< 225 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Patients with leukemias: Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
• Patients with seizure disorder may be enrolled if on a stable antiepileptic regimen for >= 14 days and well controlled.
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) except tendon reflex decreased resulting from prior therapy must be =< grade 2.
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Female patients of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method for the duration of study therapy and for at least one month after the final dose of larotrectinib. Males of reproductive potential with a non-pregnant female partner of child-bearing potential must use a highly effective contraception for the duration of the study and for at least one month after the final dose of larotrectinib. Because of the unknown risk of larotrectinib in nursing infants, nursing women should discontinue breastfeeding during treatment with larotrectinib and for 3 days following the final dose.
• Patients with solid tumors, including CNS tumors, requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. Patients with leukemia may receive systemic corticosteroids for cytoreduction up to 24 hours prior to the start of protocol therapy. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid.
• Patients who are currently receiving another investigational drug are not eligible.
• Patients who are currently receiving other anti-cancer agents are not eligible [except leukemia patients receiving corticosteroids or hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]. Patients with leukemia should receive a single dose of intrathecal cytarabine, hydrocortisone, and/or methotrexate within 7 days prior to Day 1 of Cycle 1 at the time of the baseline lumbar puncture.
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• Patients currently receiving a strong CYP3A4 inducer or inhibitor are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
• Patients with malabsorption syndrome or other conditions that significantly limit enteral absorption are not eligible.
• Patients who are unable to swallow capsules or liquid and do not have gastric access via a nasogastric or gastrostomy tube are not eligible.
• Patients who have an uncontrolled infection are not eligible.
• Patients who have received prior solid organ transplantation are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with high grade gliomas (HGG) are not eligible.
• 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.
Drug: Larotrectinib Sulfate
Central Nervous System Neoplasm, Infantile Fibrosarcoma, Recurrent Acute Leukemia, Refractory Acute Leukemia, Solid Neoplasm
Larotrectinib, TRK fusion, NTRK fusion, Infantile fibrosarcoma
A Safety and Pharmacokinetic Study of Single Agent REGN2810 in Pediatric Patients with Relapsed or Refractory Solid or Central Nervous System (CNS) Tumors and a Safety and Efficacy Trial of REGN2810 in Combination with Radiotherapy in Pediatric Patients with Newly Diagnosed Diffuse Intrinsic Pontine Glioma, Newly Diagnosed High-Grade Glioma, or Recurrent High-Grade Glioma (PNOC013)
Phase I will include children 0 years of age to <18 years of age with recurrent or refractory solid or CNS tumors. Efficacy Phase will include children and young adults ≥3 years of age and <25 years of age with newly diagnosed diffuse intrinsic pontine glioma (DIPG), newly diagnosed high-grade glioma (HGG), or recurrent HGG.
Christopher Moertel, MD
All
up to 25 Years old
Phase 1/Phase 2
NCT03690869
STUDY00004561
Key
• Age 0 to <18 years of age (Phase 1)
• Age ≥3 and ≤25 years of age (Efficacy Phase)
• Karnofsky performance status ≥50 (patients >16 years) or Lansky performance status ≥50 (patients ≤ 16 years)
• Life expectancy >8 weeks
• Adequate Bone Marrow Function
• Adequate Renal Function
• Adequate Liver Function
• Adequate Neurologic Function Key
• Patients with bulky metastatic disease of the CNS causing Uncal herniation or symptomatic midline shift, significant, symptomatic mass effect, or uncontrolled neurological symptoms such as seizures or altered mental status
• Patients with metastatic spine disease and gliomatosis as documented by diffuse involvement of >2 lobes
• Patients who are receiving any other investigational anticancer agent(s)
• Patients on greater than dexamethasone 0.1 mg/kg/day (maximum 4 mg/day) or equivalent dose in alternate corticosteroid, or actively undergoing corticosteroid dose escalation in the last 7 days
• Patients with a history of allogeneic stem cell transplant
• Prior treatment with an agent that blocks the PD-1/PD-L1/PD-L2 pathway Note: Other protocol-defined Inclusion/Exclusion criteria apply
Inclusion Criteria:
• Age 0 to <18 years of age (Phase 1)
• Age ≥3 and ≤25 years of age (Efficacy Phase)
• Karnofsky performance status ≥50 (patients >16 years) or Lansky performance status ≥50 (patients ≤ 16 years)
• Life expectancy >8 weeks
• Adequate Bone Marrow Function
• Adequate Renal Function
• Adequate Liver Function
• Adequate Neurologic Function Key
Exclusion Criteria:
• Patients with bulky metastatic disease of the CNS causing Uncal herniation or symptomatic midline shift, significant, symptomatic mass effect, or uncontrolled neurological symptoms such as seizures or altered mental status
• Patients with metastatic spine disease and gliomatosis as documented by diffuse involvement of >2 lobes
• Patients who are receiving any other investigational anticancer agent(s)
• Patients on greater than dexamethasone 0.1 mg/kg/day (maximum 4 mg/day) or equivalent dose in alternate corticosteroid, or actively undergoing corticosteroid dose escalation in the last 7 days
• Patients with a history of allogeneic stem cell transplant
• Prior treatment with an agent that blocks the PD-1/PD-L1/PD-L2 pathway Note: Other protocol-defined Inclusion/Exclusion criteria apply
Drug: cemiplimab (monotherapy), Drug: cemiplimab (maintenance), Radiation: Conventional or hypofractionated, Radiation: Re-irradiation
Relapsed Solid Tumor, Refractory Solid Tumor, Relapsed Central Nervous System Tumor, Refractory Central Nervous System Tumor, Diffuse Intrinsic Pontine Glioma, High Grade Glioma
Newly Diagnosed, Recurrent, Refractory
SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) Trial (SHARP)
This is a sham-controlled, single blinded with a blinded outcome assessment, multi-center, randomized clinical trial of endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) for the treatment of recurrent acute pancreatitis (RAP) with pancreas divisum. ERCP with miES is often offered in clinical practice to patients with RAP, pancreas divisum, and no other clear risk factors for their acute pancreatitis episodes. We hypothesize that obstruction at the level of the minor papilla is one cause of RAP in pancreas divisum; miES will relieve the obstruction, thereby reducing the risk of a recurrent attack(s) of acute pancreatitis.
Martin Freeman
All
18 Years and over
N/A
NCT03609944
STUDY00004817
Inclusion Criteria:
• Patient must consent to be in the study and must have signed and dated an approved consent form.
• >18 years
• Two or more episodes of acute pancreatitis, with each episode meeting two of the following three criteria:
• abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back)
• serum lipase activity (or amylase activity) at least three times greater than the upper limit of normal
• characteristic findings of acute pancreatitis on CECT, MRI or transabdominal ultrasonography
• At least one episode of acute pancreatitis within 24 months of enrollment
• Pancreas divisum confirmed by prior MRCP that is reviewed by an abdominal radiologist at the recruiting site.
• By physician assessment, there is no certain explanation for recurrent acute pancreatitis.
• Subjects must be able to fully understand and participate in all aspects of the study, including completion of questionnaires and telephone interviews, in the opinion of the clinical investigator
Exclusion Criteria:
• Prior minor papilla therapy (endoscopic or surgical)
• Calcific chronic pancreatitis, defined as parenchymal or ductal calcifications identified on computed tomography or magnetic resonance imaging scan that is reviewed by an expert radiologist at the recruiting site.
• Main pancreatic duct stricture*
• Presence of a structural etiology for acute pancreatitis, such as anomalous pancreatobiliary union, periampullary mass, or pancreatic mass lesion on imaging*
• Presence of a local complication from acute pancreatitis which requires pancreatogram
• Regular use of opioid medication for abdominal pain for the past three months
• Medication as the etiology for acute pancreatitis by physician assessment
• TWEAK score ≥ 4
Procedure: ERCP with miES, Procedure: EUS
Pancreatitis, Pancreas Divisum, Pancreatitis, Acute, Pancreatitis Idiopathic, Pancreas Inflamed
ERCP, Endoscopic retrograde cholangiopancreatography, pancreatitis, Clinics and Surgery Center (CSC)
Cognitive Effects of Androgen Receptor (AR) Directed Therapies for Advanced Prostate Cancer.
To compare cognitive function of men with advanced prostate cancer during treatment with enzalutamide or abiraterone acetate, adjusted for associated mediators of cognitive function (quality of life, depression, pain, and fatigue).
Emmanuel Antonarakis
Male
18 Years and over
Phase 4
NCT03016741
STUDY00005745
Inclusion Criteria:
• Have diagnosis of prostate cancer and have received treatment with GnRH agonist or antagonist therapy for at least 1 month prior to enrollment.
• Willing and able to complete survey questionnaires in English without assistance through the duration of the study. This stipulation is in place because not all of the proposed quality of life or cognitive tests are available or validated in other languages.
• Age ≥ 18 years.
• Ability to understand and the willingness to sign a written informed consent document written in English that is approved by an institutional review board.
• Have either newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) or castration-resistant metastatic prostate cancer (mCRPC) and eligible to undergo treatment with abiraterone acetate (mHSPC or mCRPC) or enzalutamide (mCRPC)
• Patients may have received the following prior AR directed therapy prior to enrollment: bicalutamide, ketoconazole. Prior to enrollment, patients may have received treatment with abiraterone acetate or enzalutamide for no more than 14 days before completing baseline studies.
• Patients may have received chemotherapy for hormone-sensitive metastatic prostate cancer only, but it must not have lasted for more than 6 months. At least 12 months must have elapsed since completion of chemotherapy.
• Patients may have received prior definitive radiation therapy or surgery. At least 60 days must have elapsed since completion of definitive radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration. Enrollment during palliative radiation of ≤ 10 days, or radiation of ≤ 10 days during the duration of the study is allowed.
• Patients must be able to take oral medication.
Exclusion Criteria:
• Prior treatment with enzalutamide or abiraterone acetate for > 14 days prior to enrollment and completion of baseline tests.
• Receipt of chemotherapy for prostate or other cancer within the past 12 months with residual cognitive deficits, or receipt of chemotherapy for mCRPC. Patients/physicians planning treatment with chemotherapy during the 12 month period of the investigation are also ineligible.
• History of cognitive impairment or dysfunction, including a history of dementia, Alzheimer's disease, stroke with residual cognitive deficits, cognitive dysfunction related to alcohol or substance abuse, or cognitive dysfunction related to prior treatment for any cancer.
• Patients with a seizure history, history of recurrent falls, or known brain metastases are excluded from this clinical trial because of their poor prognosis and because of their heightened risk of seizure or progressive cognitive and/or neurologic dysfunction that would confound the evaluation.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year. Patients with cognitive dysfunction related to treatment of another malignancy, including a history of "chemo-brain", are ineligible.
• Patients taking psychotropic medications or illicit drugs that may alter cognition, concentration, or behavior. Appropriate treatment by a licensed provider with medications for depression or anxiety, including but not limited to SSRIs, SNRIs, and standard dose benzodiazepines at a stable dose, is permitted
Biological: GnRH agonist/antagonist, Drug: Prednisone, Drug: Abiraterone Acetate, Drug: Enzalutamide
Castration-Resistant Prostatic Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer, Hormone-Refractory Prostate Cancer
Clinics and Surgery Center (CSC), cognitive function, hormonal therapy, cancer survivorship, dementia, cognitive dysfunction, mild cognitive impairment