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148 Study Matches
Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?
Gisela Chelimsky - Gisela.Chelimsky@vcuhealth.org
NCT06616363
POTS sample
Inclusion Criteria:
* symptomatic ≥ 40 bpm rise in heart rate in the first 10 min of a tilt table study without a drop in blood pressure
* Clinical symptoms of orthostatic intolerance
Exclusion Criteria:
* Pregnant or breastfeeding
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic diseases
* Unstable medical conditions
* Use of narcotics
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
POST INFECTION
Inclusion Criteria:
* acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay
Exclusion Criteria:
* Pregnant or breastfeeding
* Chronic prescriptions, history of POTS or orthostatic symptoms, recent inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other unstable chronic diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
HEALTHY CONTROLS
Inclusion Criteria:
* Apparently healthy with no known chronic illnesses
Exclusion Criteria:
* Pregnant or breastfeeding
* History of POTS or orthostatic symptoms, migraines, fibromyalgia, chronic fatigue, PTSD. Functional gastrointestinal disorders, fainting, dysmenorrhea, or other chronic pain syndrome, inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic unstable diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software BEHAVIORAL: Questionnaires to be competed, BEHAVIORAL: Provide list of medication and lifetime events, BEHAVIORAL: Use phone App to record new life events, DEVICE: Will wear an activity monitor, OTHER: Periodic 24-hour urine sodium check, DIAGNOSTIC_TEST: A fMRI scan, DIAGNOSTIC_TEST: A bedside tilt test will be performed, OTHER: IV placed to collect blood samples, OTHER: Stool Sample
POTS - Postural Orthostatic Tachycardia Syndrome
PAG activation, Cardiovagal Modulation
Heuristic Tool To Improve Symptom Self-Management in Adolescents and Young Adults With Cancer
Grace Hodges - hodgesg@vcu.edu
NCT05958316
Inclusion Criteria:
* Has received at least 1 cycle of cancer treatment and is within 3 months of initial cancer diagnosis
* Receiving regularly scheduled cancer treatment and will be receiving at least three more cycles
* Reports at least 1 symptom related to cancer and/or its treatment
* Able to speak, read, and write English as required for completion of the C-SCAT and study measures
Exclusion Criteria:
\- Cognitive and/or physical inability to complete study measures. BEHAVIORAL: Computerized Symptom Capture Tool (C-SCAT) Intervention, BEHAVIORAL: Usual Care Control
Symptoms and Signs, Cancer, Childhood Cancer
Supportive Care, Symptom Management
Cardiovascular Health & Early Stress
Paula Rodriguez Miguelez - prodriguezmig@vcu.edu
NCT06557707
Inclusion Criteria:
Cohort 1
* Men and pre-menopausal women
* 18-30 years old
Cohort 2
* males and females
* 9-17 years old
Exclusion Criteria:
Cohort 1
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis
Cohort 2
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis OTHER: Childhood stress
Stress
Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)
Rachael Buckingham, BS - Rachael.buckingham@seattlechildrens.org
NCT05548283
Inclusion Criteria:
* All genders ≥ 6 years of age at Visit 1
* Documentation of a CF diagnosis
* Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
* At least one documented Pa positive culture within two years prior to Visit 1
Exclusion Criteria:
* Participant is not pregnant
* No known renal impairment or history of solid organ transplantation
* No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
* No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
* No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
* No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1 DRUG: Beta-lactam antibiotic, DRUG: Aminoglycoside
Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation
Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360
A Study to Evaluate Del-brax (Also Referred to as AOC 1020) in Participants With FSHD (FORTITUDE-3)
Avidity Biosciences, Inc. - medinfo@aviditybio.com
NCT07038200
Inclusion Criteria:
* Clinical and genetic diagnosis of FSHD1 or FSHD2
* Ability to walk independently at pre-specified walking speed (orthoses and ankle braces allowed) for at least 10 meters at screening
* Adequate muscle strength based on QMT composite score
Exclusion Criteria:
* Breastfeeding, pregnancy, or intent to become pregnant during the study
* Unwilling or unable to comply with contraceptive requirements
* Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
* Blood Pressure \> 140/90 mmHg at Screening
* Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of the drug, whichever is longer
* Treatment with an oligonucleotide within 9 months of Screening DRUG: AOC-1020, DRUG: Placebo
Facioscapulohumeral Muscular Dystrophy, FSHD, FSHD - Facioscapulohumeral Muscular Dystrophy, FSHD1, FSHD2, Fascioscapulohumeral Muscular Dystrophy, Fascioscapulohumeral Muscular Dystrophy Type 1, Fascioscapulohumeral Muscular Dystrophy Type 2, Facioscapulohumeral Muscular Dystrophy 1, Facioscapulohumeral Dystrophy, Facio-Scapulo-Humeral Dystrophy, Facioscapulohumeral Muscular Dystrophy 2, Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1), FSH Muscular Dystrophy, Landouzy Dejerine Dystrophy, Landouzy-Dejerine Muscular Dystrophy, Landouzy-Dejerine Syndrome
Avidity, Avidity Biosciences, del-brax, del brax, delbrax, AOC1020, AOC 1020, delpacibart braxlosiran, FORTITUDE-3, FORTITUDE Phase 3, FORTITUDE, FORTITUDE 3
TIDES 2.0: Prevalence and Longitudinal Course of Depression, Anxiety, and Behavior Problems in Children With Cystic Fibrosis Under 12 Years of Age (TIDES 2)
Beth A Smith, MD - balucas@buffalo.edu
NCT07048574
Inclusion Criteria:
• Child with a diagnosis of Cystic fibrosis (CF) actively followed by the CF care team at a participating site
• Child is age 18 months thru 11 years
• English and/or Spanish speaking
• Parent/legal guardian willing and able to give informed consent, and for minor participants ages 7 thru 11 years able to give assent.
Exclusion Criteria:
* Unable or unwilling to participate in study procedures, or at Site PI discretion. Cystic Fibrosis (CF)
Cystic Fibrosis, Children, Mental health screening, Depression, Anxiety, CFTR modulators, Neuropsychiatric adverse events
A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
ctrrecruit@vcu.edu
NCT06124157
Inclusion Criteria:
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria:
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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 PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Imatinib, DRUG: Leucovorin, DRUG: Mercaptopurine, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Pegaspargase, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine
B Acute Lymphoblastic Leukemia
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
ctrrecruit@vcu.edu
NCT05304585
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).
* Patients must be =\< 21 years at the time of enrollment.
* Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients.
* All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.
* Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
* Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.
* Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.
* Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.
* Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
* Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. 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 performance score.
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment).
* Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:
* Age: 1 month to \< 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female)
* Age: 6 months to \< 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female)
* Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
* Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
* Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
* Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female)
* Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female)
* Age \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age.
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
* Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
* Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
* Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
* Evidence of uncontrolled infection.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. PROCEDURE: Biopsy Procedure, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, PROCEDURE: Magnetic Resonance Elastography, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, DRUG: Vincristine
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma
Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
NCT05489887
Inclusion Criteria:
• Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:
• Subjects with newly diagnosed neuroblastoma with INRGSS Stage M disease with either of the following features:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• 365 days to ≥ 547 days of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or the presence of any segmental chromosome aberration (SCA) (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q); OR
• Age \> 547 days of age regardless of biologic features Subjects with newly diagnosed neuroblastoma with INRGSS Stage MS disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 365 days to ≥ 547 days (18 months) of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or SCA as above Subjects with newly diagnosed neuroblastoma INRGSS Stage L2 disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 18 months to \<5 years of age without MYCN amplification, but with unfavorable histology (INPC); OR
• ≥5 years of age without MYCN amplification, but with undifferentiated or poorly differentiated INPC Subjects with newly diagnosed neuroblastoma INRGSS Stage L1 disease that is incompletely resected with MYCN amplification. Subjects \> 547 days of age initially diagnosed with INRGSS Stage L1, L2 or MS disease who progressed to Stage M without prior chemotherapy may enroll within 4 weeks of progression to Stage M. Subjects ≥ 365 days of age initially diagnosed with MYCN amplified INRGSS Stage L1 disease who progress to Stage M without systemic therapy may enroll within 4 weeks of progression to Stage M.
• Subjects must be age ≤ 21 years at initial diagnosis.
• Subjects must be \>12 months of age at enrollment.
• Adequate cardiac function defined as:
• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
• Adequate liver function must be demonstrated, defined as:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
• ALT (SGPT) \< 5 x upper limit of normal (ULN) for age
• Subjects must have adequate renal function defined as an estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
• A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)
• Both male and female post-pubertal study subjects must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of \<1% per year when used consistently and correctly) from the time of informed consent until 6 months after study treatment discontinuation. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence.
• Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
• Subjects who are less than 1 year of age
• Subjects who are 12-18 months of age with INRGSS Stage M and all stage L2 subjects with favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index \> 1) are not eligible.
• Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy.
• Treatment with immunosuppressive treatment (topical, inhaled and short-term emergency steroids excluded) within 4 weeks prior to enrollment
• Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry \< 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
• Subjects receiving any investigational drug concurrently.
• Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
• Subjects with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of investigational medicinal products (IMPs) or to significantly increase the severity of the toxicities experienced from trial treatment.
DRUG: Naxitamab
High-risk Neuroblastoma
naxitimab, induction
Pulmonary Hypertension Association Registry (PHAR)
Elizabeth Joseloff, PhD - PHAR@PHAssociation.org
NCT04071327
Inclusion Criteria:
* All age groups
* Written informed consent
* Pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), or pediatric PH due to developmental lung disease
* Within 6 months of first outpatient visit at a PH Care Center
Exclusion Criteria:
* Diagnosis of WSPH Group 2 pulmonary hypertension
* Diagnosis of WSPH Group 3 pulmonary hypertension, except PH due to developmental lung disease
* Diagnosis of WSPH Group 5 pulmonary hypertension Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Hypertension
Peer Support for Adolescents and Emerging Adults With Sickle Cell Pain (PRESENCE)
Steffi Siebert, MPH - presencestudy@pitt.edu
NCT06374238
Inclusion Criteria:
• Aged 16 to 30 years of age at time of enrollment
• Sickle Cell Disease diagnosis of any genotype based on referral or documentation
• Reports chronic pain (≥4 days/week for past 3 months or more) OR A) Being prescribed pain medication to be taken (≥4 days/week for past 3 months or more) OR B) Taking pain medication (≥4 days/week for past 3 months or more) OR C) Receiving non-pharmaceutical pain treatment (≥4 days/week for past 3 months or more)
• Access to an iOS or Android mobile device with internet access
Exclusion Criteria:
• Unable to speak or read English
• Prior hematopoietic stem cell transplant for sickle cell disease
BEHAVIORAL: CBT+ Health coach, BEHAVIORAL: CBT w/o Health Coach ( self-guided), BEHAVIORAL: Usual Care
Pain, Sickle Cell Disease
Sickle Cell Disease, Pain management, Cognitive Behavioral Therapy, Wellness
A Study to Find Out How EMPAgliflozin is Tolerated and if it Helps Children and Adolescents With Chronic KIDNEY Disease (EMPA-KIDNEY® Kids)
Boehringer Ingelheim - clintriage.rdg@boehringer-ingelheim.com
NCT07107945
Inclusion Criteria:
* Signed and dated written informed consent provided by the patient's parent(s) (or legal guardian) and patient's assent in accordance with international council for harmonisation good clinical practice (ICH-GCP) and local legislation prior to admission to the trial (informed assent will be sought according to the patient's age, level of maturity, competence, and capacity).
* Age 2 to 17 years at screening Visit 1.
* Chronic kidney disease (CKD) of any underlying aetiology defined by (as measured by central laboratory at screening Visit 1): estimated glomerular filtration rate (eGFR) (U25Crea) ≥20 to \<90 mL/min/1.73 m2 with a urine-albumine-creatinine (UACR) ≥300 mg/g
* Participants must be on a stable dose of maximally tolerated standard of care (SoC) therapy for 30 days before screening visit 1 with no plans to change the dose throughout the duration of the placebo-controlled duration of the trial. SoC is anticipated to include a single Renin-angiotensin-aldosterone system (RAAS) inhibitor, such as angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) as appropriate and tolerated. Additional use of a mineralocorticoid receptor antagonist (MRA, including finerenone if available) is permitted if needed and the dose is stable for 30 days before screening Visit 1 and no planned dose changes for the placebo-controlled portion of the trial.
* Participants receiving daily immunosuppressive therapy for an underlying immunological cause of CKD must be on a stable dose for the duration specified for each drug prior to screening and must remain on a stable regimen throughout the placebo-controlled portion of the trial.
* Further inclusion criteria apply.
Exclusion Criteria:
* Confirmed type 1 or type 2 diabetes mellitus.
* History of ketoacidosis within 8 weeks prior to Visit 1 and up to randomisation.
* Chronic dialysis or functioning kidney transplant or scheduled for transplantation throughout the duration of the trial.
* Diagnosis of uncontrolled metabolic bone disease (at the Investigator's discretion).
* Body mass index (BMI) ≤10th percentile for children ≥4 years of age and ≤25th percentile for children \<4 years of age according to Centers for Disease Control and Prevention (CDC) growth chart at screening Visit 1.
* Gastrointestinal disorders that might interfere with trial drug absorption according to investigator assessment.
* Presence of acute or active urinary tract infection (UTI) with signs or symptoms of an active UTI or therapeutic treatment for an active UTI within 14 days before screening Visit 1.
* Severe, uncontrolled hypertension (based on investigator's judgement).
* Further exclusion criteria apply. DRUG: Empagliflozin, DRUG: Placebo
Chronic Kidney Disease
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
ctrrecruit@vcu.edu
NCT06401330
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
* Patients must be \< 30 years old at enrollment.
* Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
* Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
* Patients must enroll on AREN2231 by Day 14.
* Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
* All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
* Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
* Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
* Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
* Karnofsky performance status must be ≥ 50 for patients \> 16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
* Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
* Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
* Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
* Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* 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 with a diagnosis of Stage V Bilateral Wilms Tumor.
* Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
* Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
* Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
* Notes:
* In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
* WT Predisposing Conditions:
* A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
* Unilateral multicentric WT
* Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
* Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
* Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different 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. PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Nephrectomy, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage I Mixed Cell Type Kidney Wilms Tumor, Stage II Mixed Cell Type Kidney Wilms Tumor, Stage III Mixed Cell Type Kidney Wilms Tumor, Stage IV Mixed Cell Type Kidney Wilms Tumor
Health indicators, training, and performance among ultra-endurance athletes
Alexandra Lempke - alexandra.lempke@vcuhealth.org
Alexandra Lempke
HM20031840
HM20031840
Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
Alexandra Lempke - Alexandra.Lempke@vcuhealth.org
NCT06533865
Inclusion Criteria:
For FHA and controls:
* Female, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
* For women of reproductive age, agree to use an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no evidence of systemic skeletal effects) for the study duration
* Biochemical criteria:
* Negative βHCG (pregnancy test)
* TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
* Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
* eGFR ≥ 30ml/minute
* If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
Additional inclusion criteria for FHA:
* Less than 3 menses in the preceding 6 months
* BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
* Dental check-up within the past year
* If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.
Exclusion Criteria:
For FHA and controls
* Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
* Use of bisphosphonates
* Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
* Current use of systemic corticosteroids
* Migraine with aura.
* Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
* Active substance use disorder; current smoker
* History of malignancy or Paget disease of bone
* Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
Additional exclusion criteria for FHA
* Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
* Immunodeficiency or taking immunosuppressive therapy
* Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency
* Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
* Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
* Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
* Concerning EKG findings for ischemia
Additional exclusion criteria for normal-weight healthy controls
• BMD Z-score \<-2.5 (who we will refer for evaluation) DRUG: Romosozumab, DRUG: Placebo, DRUG: Zoledronic acid
FHA (Functional Hypothalamic Amenorrhea)
The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial (DIVA)
Elizabeth Foglia - FOGLIA@email.chop.edu
NCT05446272
Inclusion Criteria:
* Gestational age of 23 0/7- 28 6/7 weeks at birth
* Intubated in the first 7 days of life
* Undergoing extubation following at least 12 hours of invasive mechanical ventilation
* Post-natal age \<32 weeks Post menstrual age at time of extubation
Exclusion Criteria:
* Major congenital anomalies, including pulmonary hypoplasia
* Neurologic disorders affecting respiratory drive (other than apnea of prematurity)
* Esophageal bleeding or other contraindication to NG/OG catheter placement
* Current weight \<500 grams (based on Edi catheter approval)
* Study ventilator not available at time eligibility criteria are met
* Planned surgery or invasive procedure within 5 days of extubation
* Informed consent not provided DEVICE: NIV-NAVA, DEVICE: NS-NIPPV
Extubation Failure, Bronchopulmonary Dysplasia, Death
Optimal Ventilation for Cardiac Arrest (OPTI-VENT)
CHOP RSC Clinical Research Program Manager - grahamk1@chop.edu
NCT07114510
Inclusion Criteria:
* Invasive airway in place at the start of CPR or airway placed within the first 5 minutes
* Received at least 1 minute of CPR.
Exclusion Criteria:
* Lack of commitment to aggressive ICU therapies (e.g., CPR performed as part of end-of-life care.
* Brain death determination prior to the CPR event.
* Out-of-hospital cardiac arrest was the reason for initial admission to the hospital (known poor outcomes).
* Supported by Veno-Arterial Extra Corporeal Membrane Oxygenation at the start of CPR OTHER: OPTI-VENT Bundle, OTHER: Transition, OTHER: None - control
Cardiac Arrest (CA)
Pediatric
US National OCS Heart Perfusion (OHP) Registry
Raicca Haqqi - rhaqqi@transmedics.com
NCT05915299
Inclusion Criteria:
* N/A
Exclusion Criteria:
* N/A DEVICE: OCS Heart
Heart Transplant
Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia (ORION-20)
Novartis Pharmaceuticals - novartis.email@novartis.com
NCT06597019
Inclusion Criteria:
* Male or female participants, 6 to \<12 years of age at screening
* HeFH diagnosed either by genetic testing or on phenotypic criteria
* Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening
* For participants 8 to \<12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants \<8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
* Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.
Exclusion Criteria:
* Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
* Homozygous familial hypercholesterolemia (HoFH)
* Body weight \<16 kg at the screening and/or randomization (Day 1) visit
* Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation \>3x ULN, or total bilirubin elevation \>2x ULN (except patients with Gilbert's syndrome)
* Pregnant or nursing females
* Recent and/or planned use of other investigational medicinal products or devices DRUG: Inclisiran, DRUG: Placebo
Familial Hypercholesterolemia - Heterozygous
Heterozygous familial hypercholesterolemia (HeFH),, LDL-cholesterol (LDL-C),, Children,, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Heterozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Heart Failure,, Cardiovascular Diseases,, Cholesterol,, Aortic Stenosis
Multisite Inventory of Neonatal-Perinatal Interventions (MINI) Minimum Dataset
Matthew A Rysavy, MD, PhD - Matthew.A.Rysavy@uth.tmc.edu
NCT05685745
Inclusion Criteria:
* All local births with gestational ages of 22 weeks 0 days - 23 weeks 6 days, regardless of pregnancy outcome or neonatal intensive care (NICU) admission; AND
* All outborn NICU admissions with gestational age at birth of 22 weeks 0 days - 23 weeks 6 days
* Optional: Centers who desire to include data for NICU admissions of infants born \<22 weeks' gestation may also submit these data. Infant, Extremely Premature, Obstetric Labor, Premature, Premature Birth, Intensive Care, Neonatal, Intensive Care Units, Neonatal
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
Gwen Nichols, MD - gwen.nichols@lls.org
NCT05183035
Inclusion Criteria
* Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/Blood Cancer United territory).
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
• Children, adolescents, and young adults with AML without demonstrated FLT3/internal tandem duplication (ITD) mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment.
• And participants must have AML which is either: * Untreated second relapse, in participants who are sufficiently fit to undergo another round of intensive chemotherapy, or * Untreated first relapse, in participants who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). * Participants 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 start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• 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 before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]); * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial. * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the participant will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving an investigational drug other than those specified for this study. * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV) infection. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90-days after last exposure to any other chemotherapy, whichever is longer. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Children, adolescents, and young adults with AML without demonstrated FLT3/internal tandem duplication (ITD) mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment.
• And participants must have AML which is either: * Untreated second relapse, in participants who are sufficiently fit to undergo another round of intensive chemotherapy, or * Untreated first relapse, in participants who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). * Participants 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 start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• 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 before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]); * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial. * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the participant will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving an investigational drug other than those specified for this study. * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV) infection. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90-days after last exposure to any other chemotherapy, whichever is longer. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Azacitidine, DRUG: Venetoclax
Acute Myeloid Leukemia
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
The Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease (LIBRA)
Trial Transparency email recommended (Toll free for US & Canada) - contact-us@sanofi.com
NCT06975865
Inclusion Criteria:
* Participants who have been diagnosed with SCD.
* Participants who have had between ≥2 to ≤10 episodes of documented acute clinical VOC within 12 months of the screening visit.
* Participants who are either not on hydroxyurea and/or L-glutamine at the Screening Visit and does not plan to receive them during the course of the study or has received HU and/or L-glutamine for a minimum of 6 months. Participants on hydroxyurea and/or L-glutamine must have been on a stable weight-based dose level (mg/kg) for at least 3 months prior to the Screening Visit, with the intent to continue at the same weight-based dose level for the duration of the study, except for safety reasons.
* Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* For participants ≥10 to \<18 years of age: the parent(s)/legal guardian(s) must provide written informed consent prior to any study-related procedures being performed.
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply: Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
* Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.
* Participants with history of stroke, or history of abnormal transcranial doppler.
* Participants with uncontrolled or active HBV infection and/or HCV infection including those receiving antiviral therapy at the time of screening.
* HIV infection.
* A history of active or latent tuberculosis (TB)
* Positive COVID-19 molecular test.
* Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days and/or voxelotor (OXBRYTA®) within 30 days prior to the Screening visit.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. DRUG: Rilzabrutinib, DRUG: Placebo
Sickle Cell Disease
A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
NCT06679140
Inclusion Criteria:
• 12 to \<18 years of age, weighing at least 40 kg, or ≥18 years of age of any weight at screening.
• Presence of risk factors for progression to severe COVID-19 at the time of screening based on age:
• 12 to 49 years of age with at least two risk factors, where one must be moderate immunocompromise;
• 50 to 64 years of age with at least two risk factors;
• 65 to 74 years of age with at least one risk factor;
• For participants 75 years of age or older, there are no requirements related to risk factors. The list of risk factors includes: BMI ≥35 kg/m2; Current smoker; Chronic lung disease; Cardiovascular disease; Type 1 or Type 2 diabetes mellitus; Mild to moderate renal impairment; Neurodevelopmental disorders; Sickle cell disease; Moderate immunosuppression.
• Confirmed SARS-CoV-2 infection as determined by RAT in nasal or NP specimen collected within 1 day prior to randomization. Initial onset of symptoms attributable to COVID-19 within 5 days prior to randomization and at least 1 of the specified symptoms attributable to COVID-19 present on the day of randomization. Randomization must occur no later than the 5th day, where the onset of symptoms is the first day.
• Participants must be unable or unwilling to take nirmatrelvir/ritonavir.
Exclusion Criteria:
• Current need or anticipated need for hospitalization within 24 hours, due to signs of severe COVID-19 illness (eg, SpO2 \<94% on room air, respiratory rate \>30 breaths/minute, or lung infiltrates \>50%) or due to other medical conditions requiring hospitalization in the opinion of the site investigator.
• Receiving dialysis or have known severe renal impairment \[ie, eGFR consistently \<30 mL/min/1.73 m2 for adults or CrCl \<30 mL/min for adolescents\], using the serum creatinine-based CKD-EPI formula or the Cockroft Gault, respectively.
• Active liver disease with AST or ALT \>3 ULN, Total bilirubin ≥2 × ULN (for Gilbert's syndrome, direct bilirubin \>ULN is exclusionary) within the past 3 months, or liver function impairment with Class C per Child Pugh classification.
• Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention.
• Ongoing Long COVID or Post Acute Sequelae of COVID-19 diagnosis.
• Severely immunocompromised.
• Any comorbidity requiring hospitalization and/or surgery within 7 days prior to study entry, or that is considered life threatening within 30 days prior to study entry, as determined by the investigator.
• History of hypersensitivity or other contraindication to any of the components of the study interventions.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Current use of any prohibited concomitant medication(s).
• Has received any other antiviral for the treatment of COVID-19, including remdesivir, nirmatrelvir/ritonavir, molnupiravir, or COVID-19 mAbs within 30 days or 5 half-lives \[whichever is longer\] prior to screening, or received convalescent COVID-19 plasma within 12 months.
• Received any dose of a COVID-19 vaccine within 4 months of randomization or expected to receive one through Day 34.
• Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
• Prior participation in this clinical trial or any other clinical trial of ibuzatrelvir.
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
DRUG: ibuzatrelvir, DRUG: placebo
COVID-19 SARS-CoV-2 Infection
Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, COVID-19, Viral Protease Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antiviral Agents, Anti-Infective Agents, ibuzatrelvir
Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients (BASECAMP)
Satellos Medical Information - medicalinfo@satellos.com
NCT07287189
Key
Inclusion Criteria:
* Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing with a confirmed mutation in the DMD gene.
* Male DMD patients who are ambulatory and aged ≥ 7 to \< 10 years at the time of screening.
* Stable dose of systemic glucocorticoids (i.e., prednisolone, deflazacort, or vamorolone) according to the standard of care for ≥ 3 months prior to the Screening Visit and for the duration of the trial. Patients who are not receiving glucocorticosteroids are also eligible if stopped ≥ 3 months prior to the Screening Visit.
* Stable doses of prescription medicines including ACE inhibitors, β-blockers, and diuretics (excluding glucocorticosteroids) and over-the-counter medicines and/or herbal supplements for supportive care ≥ 1 month prior to the Screening Visit and for the duration of the trial.
* Participants that have previously received delandistrogene moxeparvovec (brand name Elevidys) either in a prior clinical trial or in the commercial setting \> 18 months prior to screening whose muscle function tests have stabilized or demonstrated decline ≥ 3 months prior to Screening, as determined by investigator and documented in chart notes, will be eligible.
* Participants that have previously received an exon skipper \> 6 months prior to Screening whose muscle function tests have stabilized or demonstrated decline ≥ 3 months prior to Screening, as determined by investigator and documented in chart notes, will be eligible.
* Participants receiving a stable dose of givinostat (brand name Duvyzat) for at least 18 months or longer prior to the Screening Visit will be eligible. Participants unable to tolerate givinostat who discontinued treatment before 18 months are eligible to enroll if date of last dose is ≥ 30 days from the Screening date. Givinostat should not be discontinued, if tolerated, to meet study entry criteria.
* Participants that have received prior treatment with an investigational gene therapy product (other than delandistrogene moxeparvovec) ≥ 24 months prior to the Screening Visit.
* If participating in a physical therapy/strength training regimen, must be stable for ≥ 2 months prior to the Screening Visit and for the duration of the trial.
Key Exclusion Criteria:
* Ambulatory patients expected to experience loss of ambulation within ≤ 12 months.
* Participants for whom MRI or open muscle biopsy are contraindicated.
* Evidence of significant hepatic dysfunction, defined as GLDH \> 2X upper limit of normal (ULN) at the Screening Visit.
* Impaired cardiac function defined as a left ventricular ejection fraction of \< 50% on screening cardiac assessments (echocardiogram or MRI) or evidence of symptomatic cardiomyopathy.
* A forced vital capacity \< 60% predicted at the Screening Visit.
* Ongoing participation in any other therapeutic clinical trial or follow-up study for a therapeutic intervention
* Consumption of grapefruit juice or grapefruit containing products
* Severe behavioural or cognitive problems that preclude participation in the study, in the opinion of the investigator.
Additional entry criteria will be reviewed with the clinical site investigator. DRUG: SAT-3247, DRUG: Placebo
Duchenne Muscular Dystrophy, Duchenne, DMD, Neuromuscular Diseases, Muscular Dystrophies
muscle regeneration, satellite cell, asymmetric division, dystrophin
Testing the Addition of an Anti-Cancer Drug, Cabozantinib to the Immunotherapy Drug Cemiplimab (REGN2810), in Adolescents and Adults With Advanced Adrenocortical Cancer
ctrrecruit@vcu.edu
NCT06900595
Inclusion Criteria:
* STEP 1: Patients must have documented histologically or cytologically confirmed adrenocortical carcinoma
* STEP 1: Locally advanced unresectable or recurrent/metastatic disease
* STEP 1: Evaluable disease as defined by RECIST v 1.1
* STEP 1: Up to 3 prior lines of systemic therapy will be allowed in the unresectable/recurrent/metastatic setting. Treatment naïve patients will be allowed.
* Note: Combination etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) is considered 1 line of therapy. For patients who received mitotane ≤ 6 months prior to registration, mitotane should be discontinued 28 days prior to study registration AND a mitotane level must be documented to be \< 2 mg/L prior to registration. Patients who have received mitotane within 6 months of enrollment and who have mitotane levels ≥ 2 mg/L will not be eligible to enroll
* STEP 1: No prior treatment with cabozantinib or other cMET inhibitors, or anti-CTLA-4, or anti-PD-1/PD-L1 therapy
* STEP 1: Prior external beam radiation therapy (any area radiated within a month prior to study registration cannot be used as an index lesion and only growth outside of the radiation field can be considered for disease progression), systemic cytotoxic chemotherapy, targeted therapies will be allowed, as long as not administered within 14 days before study registration, and provided any acute treatment-related associated toxicities have recovered to ≤ grade 1 except for alopecia, peripheral neuropathy or other residual toxicities that are not deemed clinically significant
* STEP 1: Potential trial participants should have recovered from clinically significant adverse events, and wound healing is clinically adequate of their most recent therapy/intervention prior to enrollment
* STEP 1: Age 12 years and above; and BSA ≥ 1.2m\^2
* STEP 1:
* Eastern Cooperative Oncology Group (ECOG) performance 0 - 2 (age 18 and above); or
* Patients 12 to \<16 years of age will be assessed by the Lansky scale and should have a score ≥ 50; or
* Patients ≥ 16 to \<18 years of age will be assessed by the Karnofsky scale, and should have a score ≥ 50
* STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mcL without colony stimulating factor support within 2 weeks prior
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Platelet count ≥ 100,000/mcL
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Hemoglobin ≥ 8 g/dL
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* For patients with known Gilbert's disease, bilirubin ≤ 3 mg/dL
* STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)
* STEP 1: Random Urine Creatinine Ratio (UPCR) ≤ 1 mg/mg
* STEP 1: Calculated (Calc.) creatinine clearance ≥ 30 mL/min
* STEP 1: Mitotane level \< 2 mg/L\*
* Only applicable for patients who have received mitotane ≤ 6 months prior to registration
* STEP 1: Must have assessment of adrenal steroid production within 3 months prior to registration as patients will be stratified based on corticosteroid production
* Patients will be classified as corticosteroid producing if random plasma adrenocorticotropic hormone (ACTH) is \< 20 pg/mL plus random serum cortisol is \> 20 mcg/dL in the absence of anti-cortisol therapy. Patients already on anti-cortisol therapy will be classified as having corticosteroid producing tumors regardless of their plasma ACTH and serum cortisol levels, as these levels can be affected by anti-cortisol therapy
* STEP 1: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects based on animal reproduction studies. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done ≤ 14 days prior to registration is required
* STEP 1: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional within 28 days of registration. To be eligible for this trial, patients should be class II or better
* STEP 1: No known history of congenital long QT syndrome
* STEP 1: No known history of myocarditis
* STEP 1: No myocardial infarction (MI) or unstable angina within 6 months of registration
* STEP 1: No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 6 months of registration including, but not limited to: active peptic ulcer, known endoluminal metastatic lesion(s) with history of bleeding, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation
* STEP 1: No history of gastrointestinal (GI) perforation within 6 months of registration
* STEP 1: No known tumor with invasion into the GI tract from the outside causing increased risk of perforation or bleeding within 28 days of registration
* STEP 1: No current radiologic or clinical evidence of pancreatitis
* STEP 1: No history of clinically significant non-healing wounds or ulcers within 28 days of registration
* STEP 1: No uncontrolled hypertension within 14 days of registration (defined as sustained systolic blood pressure (SBP) ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg despite optimal medical management)
* STEP 1: No known endobronchial lesions involving the main or lobar bronchi and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. (CT with contrast is recommended to evaluate such lesions.). No hemoptysis greater than ½ teaspoon (2.5 mL) or any other signs of pulmonary hemorrhage within the 3 months prior to registration
* STEP 1: No history of pneumonitis
* STEP 1: No known tumor invading or encasing any major blood vessels
* STEP 1: No history of fracture within 28 days of registration
* STEP 1: No known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) before registration. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
* STEP 1: Major surgery (e.g., laparoscopic nephrectomy, GI surgery, within 2 weeks before registration. Minor surgeries within 10 days before registration. Patients with clinically relevant ongoing complications from prior surgery are not eligible
* STEP 1: Verbalizes the ability to swallow oral tablet formulation
* STEP 1: No history of allergic reaction attributed to compounds of similar chemical or biological composition to cabozantinib
* STEP 1: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen will be eligible
* STEP 1: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1: No active autoimmune disease: or history of autoimmune disease that might recur, and which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of:
* immune related neurologic disease,
* multiple sclerosis,
* autoimmune (demyelinating) neuropathy,
* Guillain-Barre syndrome (GBS), myasthenia gravis,
* systemic autoimmune disease such as systemic lupus erythematosus (SLE),
* connective tissue diseases,
* scleroderma, inflammatory bowel disease (IBD),
* Crohn's, ulcerative colitis,
* patients with a history of toxic epidermal necrolysis (TEN),
* Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease,
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible,
* Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome, and psoriasis controlled with topical medication and patients with only positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* STEP 1: No steroid use \> 10 mg prednisone equivalents daily. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy
* STEP 1: Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
* STEP 1: Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* STEP 1: Herbal supplements and traditional Chinese medicines are not allowed
* STEP 1: Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. Allowed use of anticoagulants include: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, apixaban. Also use of anticoagulants is allowed in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
* STEP 2 (CROSSOVER): Patients must have demonstrated radiographic progression of disease on cabozantinib monotherapy (Arm A) per RECIST version 1.1 criteria
* Patients must cross-over to Arm C within 4 weeks (+/- 1 week) after radiographic documented progression and do not need to have a repeat radiographic assessment prior to starting cabozantinib and cemiplimab (REGN2810). The progression CT may serve as eligibility for crossover and as the baseline tumor measurement
* STEP 2 (CROSSOVER): Patients that were discontinued on cabozantinib, or currently meet criteria for discontinuation of cabozantinib due to toxicity are not eligible to cross-over.
* Note: Patients who underwent dose reduction of cabozantinib during treatment on Arm A will not re-escalate dose at or after cross-over to Cabo-Cemiplimab (REGN2810) (Arm B)
* STEP 2 (CROSSOVER): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done ≤ 14 days prior to re-registration is required PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib, BIOLOGICAL: Cemiplimab, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging
Locally Advanced Adrenal Cortical Carcinoma, Metastatic Adrenal Cortical Carcinoma, Recurrent Adrenal Cortical Carcinoma, Stage III Adrenal Cortical Carcinoma AJCC v8, Stage IV Adrenal Cortical Carcinoma AJCC v8, Unresectable Adrenal Cortical Carcinoma
Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer
ctrrecruit@vcu.edu
NCT06513962
Inclusion Criteria:
* \< 40 years of age at the time of enrollment
* Patient must be a post-menarchal female and report that their initial menstrual period occurred \> 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)
* Newly diagnosed with first cancer, exclusive of breast cancer.
* Note: Apart from breast carcinoma, other tumor types originating in the breast are permitted (e.g., sarcoma, lymphoma).
* Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.
* For patients \< 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m\^2 cumulative cyclophosphamide equivalent dose (CED). For patients ≥ 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.
* 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:
* Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
* Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
* Congenital syndromes associated with infertility and decreased ovarian reserve at baseline. For example: Turner's Syndrome, Fragile X premutation carriers, Down syndrome, etc.
* Pre-existing seizure disorder, congenital long QT syndrome, pseudotumor cerebri; history of pulmonary embolism, venous thrombosis, or myocardial infarction. Note: Contact study chairs if questions arise about other pre-existing conditions.
* Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
* Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted prior to study enrollment.
* Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).
* Patients who are pregnant are not eligible. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants for the duration of triptorelin therapy (24 weeks per dose).
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of triptorelin therapy (24 weeks per dose). OTHER: Best Practice, PROCEDURE: Biospecimen Collection, OTHER: Electronic Health Record Review, OTHER: Survey Administration, DRUG: Triptorelin Pamoate
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease (AXemplify-357)
Incyte Corporation Call Center (US) - medinfo@incyte.com
NCT06585774
Inclusion Criteria:
* ≥ 12 years of age at the time of informed consent.
* New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
* History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.
* Adequate hematologic function with ANC ≥ 0.5 × 109/L independent of growth factors for at least 7 days prior to study entry.
* Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
* Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
* Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
* Received more than 7 days of systemic corticosteroid treatment for cGVHD or unable to begin a prednisone dose ≥ 1.0 mg/kg per day (or methylprednisolone equivalent) for cGVHD.
* Received previous systemic treatment for cGVHD, including extracorporeal photopheresis.
* Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
* Prior treatment with CSF-1R targeted therapies.
* Active, uncontrolled bacterial, fungal, parasitic, or viral infection.
* Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-HCT was performed, including DLIs for the treatment of molecular relapse.
* History of acute or chronic pancreatitis.
* Active symptomatic myositis.
* History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease.
* Severe renal impairment, that is, estimated CrCl \< 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or endstage renal disease on dialysis.
* Impaired liver function, defined as total bilirubin \> 1.5 × ULN and/or ALT and AST \> 3 × ULN in participants with no evidence of liver cGVHD.
* Pregnant or breastfeeding.
Other protocol-defined Inclusion/Exclusion Criteria may apply. DRUG: INCA034176, DRUG: Placebo, DRUG: Corticosteroids
Chronic Graft-versus-host-disease
cGVHD
Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia
ctrrecruit@vcu.edu
NCT06317662
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
* Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age at the time of enrollment
* Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
* Diagnostic immunophenotype: Leukemia cells must express CD19
Exclusion Criteria:
* Patients with Down Syndrome
* Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
* Steroid pretreatment:
* PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
* Inhaled and topical steroids are not considered pretreatment
* Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
* Intrathecal cytarabine or methotrexate:
* An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
* Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
* Hydroxyurea:
* Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
* 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: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin, DRUG: Dexamethasone, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, PROCEDURE: FDG-Positron Emission Tomography, DRUG: Leucovorin, DRUG: Levoleucovorin, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Methylprednisolone, PROCEDURE: Multigated Acquisition Scan, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Therapeutic Hydrocortisone, DRUG: Thioguanine, DRUG: Venetoclax, DRUG: Vincristine
Acute Leukemia of Ambiguous Lineage, B Acute Lymphoblastic Leukemia