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The Efficacy and Safety of Rilzabrutinib in Participants 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 and ≤10 episodes of documented clinical VOC within 12 months of the screening events.
* 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
A Study to Investigate the Safety, Tolerability, and Efficacy of SAR446268, an Adeno-associated Viral Vector-mediated Gene Therapy in Participants Aged 10 to 55 Years of Age With Non-congenital Myotonic Dystrophy Type 1 (BrAAVe)
Trial Transparency email recommended (Toll free for US & Canada) - contact-us@sanofi.com
NCT06844214
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
* For Part A, participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
* For Part B, participants must be as follows:
* 10 to 17 years of age inclusive, at the time of signing the informed consent or,
* 18 to 55 years of age inclusive, at the time of signing the informed consent.
* Participants with non-congenital onset DM1
* Participants presenting with signs of DM1 including myotonia and muscle weakness, as diagnosed previously by a clinician based on medical history.
* Participants with genetic diagnosis of DM1 \[cytosine-thymine-guanine (CTG) repeat length ≥50 in one allele from medical history\]
* Participants who can walk independently for at least 10 meters at screening (orthoses and ankle braces allowed).
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Participants with neutralizing antibodies against the AAV.SAN011 capsid
* Participants with left ventricular ejection fraction \<50%
* Participants with liver or biliary disease defined as having at least one of the following:
* ALT \>3 x ULN and AST \>3 x ULN
* Alkaline phosphatase \>3 x ULN
* Total bilirubin \>1.5 x ULN (unless has a genetically confirmed diagnosis of Gilbert's syndrome)
* Direct bilirubin ≥1.5 x ULN
* Participants with International normalized ratio \>1.5
* Participants with renal disease defined as:
• Serum creatinine \>1.5 x ULN and/or estimated glomerular filtration rate \<60 mL/min/1.73 m2 as determined by Chronic Kidney Disease Epidemiology Collaboration (2021) for those age ≥18 years and Bedside Schwartz Equation for those \<18 years
* Participants with chronic respiratory insufficiency and on long term/hull-time ventilatory assistance requiring at least 6 hours per day for at least 21 consecutive days.
* Participants with contraindication to corticosteroid or with conditions that could worsen in the presence of corticosteroids, as determined by the Investigator.
* Participants with active hepatitis B or C infection; HBsAg (+), or HCV RNA (+), or current antiviral therapy for either.
* Participants with HBcAb (+) who are not amenable for prophylactic anti-HBV therapy or pre-emptive therapy guided by serial HBV DNA monitoring during the corticosteroids therapy.
* Participants at high risk for tuberculosis reactivation during the corticosteroids therapy as determined by the Investigator.
* Participants with a known HIV infection
* Participants with serious intercurrent illness that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival.
* Participants with recent history of or current drug or alcohol abuse in the past 12 months prior to screening.
* Participants with history of tibialis anterior biopsy within 12 weeks from Day 1 or planning to undergo tibialis anterior biopsies during the duration of this clinical trial.
* Participants with significant developmental delay, intellectual disability, or behavioral neuropsychiatric manifestations as determined by the Investigator.
* Participants with previous systemic corticosteroids treatment at doses of \>5 mg/day within 15 days of Day 1
* Participants with previous treatment with anti-myotonic medication within 15 days of Day 1
* Participants not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
* Participants who have been classified as severe cardiac risk by the Investigator.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. BIOLOGICAL: SAR446268
Myotonic Dystrophy
Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
NCT06541262
Inclusion Criteria:
• Age: Less than 30 years old at initial diagnosis
• Pathology All subjects must have a confirmed diagnosis of tumor type. Phase I: Relapsed/refractory solid tumors: Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma Phase II: * Relapsed/refractory Neuroblastoma * Relapsed/refractory Ewing sarcoma
• Tumor assessment: Disease assessment is required for eligibility and must be done after last dose of previous therapy and prior to first dose of study drug.
• Disease Status: Relapsed/Refractory Neuroblastoma Relapsed disease defined as neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) and has now relapsed and is in any number of relapses. Refractory disease defined as High-risk neuroblastoma (as defined by INRG) that failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy, progression during upfront therapy or with disease remaining after standard immunotherapy. International Neuroblastoma Risk Group Staging System (INRG) High Risk NB defined as one of the following:
• Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification
• Age ≥ 547 days and INRG Stage M regardless of biologic features
• Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to Stage M without systemic chemotherapy
• Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy Relapsed/refractory Sarcoma Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for sarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.
• Measurable or evaluable disease, including at least one of the following: * Measurable tumor by CT or MRI * MIBG or PET that is positive for disease * Bone Marrow biopsy/aspirate that is positive for disease
• Timing from prior therapy: Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer therapy and be within the following timelines:
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study.
• Small Molecule Inhibitors (anti-neoplastic agent): At least 2 weeks from the completion of therapy with a small molecule inhibitor.
• Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells, anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.).
• Radiotherapy: At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
• Stem Cell Transplant: * Allogeneic: No evidence of active graft vs. host disease * Allogeneic/Autologous: ≥ 2 months must have elapsed since transplant.
• MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
• Subjects must have a Lansky or Karnofsky Performance Scale score of \>/= 50.
• Subjects must have adequate organ function at the time of enrollment: * Cardiac: Subjects must have a QTcF ≤ 480 msc. * Hematological: Hematological recovery as defined by ANC ≥750/μL * Liver: Adequate liver function as defined by AST and ALT \<5x upper limit of normal * Renal: Subjects must have adequate renal function defined as: * estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (for subjects \< 17 years old) (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr * estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (for subjects ≥17 years old (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr) * OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
• Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.
• Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).
Exclusion Criteria:
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior therapy.
• Subjects who are currently receiving Vitamin K antagonists (warfarin).
• Subjects who are currently receiving the class of lipid-lowering medications HMG-CoA reductase inhibitors (statins).
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
• Subjects with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the subject's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.
• Subjects with any of the following gastrointestinal disorders:
• Active malabsorption (e.g. short gut) syndrome.
• Uncontrolled diarrhea (excess of 4 stools/day)
• Gastritis, ulcerative colitis, Chron's disease or hemorrhagic coloproctitis
• History of gastric or small bowel surgery involving any extent of gastric or small bowel resection
• Lactating subjects are not eligible unless they have agreed to not breastfeed their infants. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing subject with silmitasertib. (NOTE: breast milk cannot be stored for future use while the nursing subject is being treated on study.)
• Subjects with a history of any other malignancy.
DRUG: Silmitasertib, DRUG: Irinotecan, DRUG: Temozolomide, DRUG: Vincristine
Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma
A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
Boehringer Ingelheim - clintriage.rdg@boehringer-ingelheim.com
NCT07220083
Inclusion criteria:
• Male or female participants ≥12 years old on the day of signing informed consent/assent (Visit 1)
• Weight of ≥40 kg at the screening visit (Visit 1)
• Body mass index (BMI) of ≤40 kg/m² at the screening visit (Visit 1)
• Participants with a diagnosis prior to the screening visit (Visit 1) of either: * Biopsy-confirmed primary focal segmental glomerulosclerosis (pFSGS) (based on Investigator's judgement) OR * Genetic focal segmental glomerulosclerosis (FSGS) resulting from a gain-of-function mutation in the transient receptor potential cation subfamily C member 6 (TRPC6) gene (based on historical genetic test)
• Urine protein-creatinine ratio (UPCR) ≥1500 mg/g based on the mean of the spot urine sample and first morning void urine sample (both assessed by central laboratory) at the screening visit (Visit 1)
• Estimated glomerular filtration rate (eGFR) * For adult participants (≥18 years): ≥25 mL/min/1.73 m² (chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on combined serum creatinine plus cystatin C) at the screening visit (Visit 1) * For adolescent participants (12 to \<18 years); ≥25 mL/min/1.73 m² based on chronic kidney disease under 25 years (CKiD U25) formula using height and serum cystatin C at the screening visit (Visit 1) Further inclusion criteria apply. Exclusion criteria:
• Known monogenic or syndromic causes of FSGS (with the exception of TRPC6 gain-of-function gene mutations)
• Clinical or histologic evidence of secondary maladaptive or toxic forms of FSGS (based on Investigator's judgement)
• FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigator's judgement)
• A history of organ transplantation or planned organ transplantation during the course of the trial
• Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) Further exclusion criteria apply.
• Male or female participants ≥12 years old on the day of signing informed consent/assent (Visit 1)
• Weight of ≥40 kg at the screening visit (Visit 1)
• Body mass index (BMI) of ≤40 kg/m² at the screening visit (Visit 1)
• Participants with a diagnosis prior to the screening visit (Visit 1) of either: * Biopsy-confirmed primary focal segmental glomerulosclerosis (pFSGS) (based on Investigator's judgement) OR * Genetic focal segmental glomerulosclerosis (FSGS) resulting from a gain-of-function mutation in the transient receptor potential cation subfamily C member 6 (TRPC6) gene (based on historical genetic test)
• Urine protein-creatinine ratio (UPCR) ≥1500 mg/g based on the mean of the spot urine sample and first morning void urine sample (both assessed by central laboratory) at the screening visit (Visit 1)
• Estimated glomerular filtration rate (eGFR) * For adult participants (≥18 years): ≥25 mL/min/1.73 m² (chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on combined serum creatinine plus cystatin C) at the screening visit (Visit 1) * For adolescent participants (12 to \<18 years); ≥25 mL/min/1.73 m² based on chronic kidney disease under 25 years (CKiD U25) formula using height and serum cystatin C at the screening visit (Visit 1) Further inclusion criteria apply. Exclusion criteria:
• Known monogenic or syndromic causes of FSGS (with the exception of TRPC6 gain-of-function gene mutations)
• Clinical or histologic evidence of secondary maladaptive or toxic forms of FSGS (based on Investigator's judgement)
• FSGS of undetermined cause (FSGS-UC) with a diagnosis prior to the screening visit (Visit 1) (based on Investigator's judgement)
• A history of organ transplantation or planned organ transplantation during the course of the trial
• Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the last 6 months prior to screening (Visit 1) Further exclusion criteria apply.
DRUG: BI 764198, DRUG: Placebo
Focal Segmental Glomerulosclerosis
A Hospital-based Intervention for Youth Injured Through Violence
Nicholas Thomson - nthomson2@vcu.edu
NCT07475247
Youth participant inclusion criteria:
* Aged 13-17 years old
* English speaking
Youth participant exclusion criteria:
* Youth aged \<13 years and \>17 years old
* Non-English speaking
* Youth of caregivers younger than 18 years old
Adult/caregiver participant inclusion criteria:
\- Aged 18 years or older
Adult/caregiver participant exclusion criteria:
\- Aged younger than 18 years
OTHER: Elevate Virtual Reality (VR), OTHER: Assessement completion
Violence
Virtual Reality, Fire-arm violence among youth
Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Trial Registration Coordinator - clinicaltrials@cslbehring.com
NCT06699849
Inclusion Criteria:
* At the time of informed consent:
* 18 years of age (adults); or
* 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\])
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
Exclusion Criteria:
* VOC pain onset greater than (\>) 72 hours before administration of first parenteral opioid.
* Must not have a history of \> 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation.
* Serum hemoglobin \< 6 g/dL, serum ferritin ≥ 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine. BIOLOGICAL: CSL889, DRUG: Placebo
Sickle Cell Disease Vaso-occlusive Crisis
Sickle cell disease, Acute kidney injury, Pharmacokinetics, Acute chest syndrome, Vaso-occlusive crisis, Hemopexin
Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT) (KESETT)
Megan Wardius - mew5j@virginia.edu
NCT06907173
Inclusion Criteria:
* The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
* The patient received an adequate dose of benzodiazepines. The doses may be divided.
* The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
* Continued or recurring seizures in the Emergency Department.
* Age 1 years or older
* Known or estimated weight ≥10 Kg
Exclusion Criteria:
* Known pregnancy
* Prisoner
* Opt-out identification or otherwise known to be previously enrolled in KESETT
* Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
* Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
* Endotracheal intubation prior to enrollment
* Acute traumatic brain injury clearly precedes seizures
* Scalp injury or burn preventing EEG placement
* Known allergy or other known contraindication to KET or LEV
* Hypoglycemia \< 50 mg/dL
* Hyperglycemia \> 400 mg/dL
* Cardiac arrest / post-anoxic seizures DRUG: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg)
Status Epilepticus
Catheter-Related Early Thromboprophylaxis With Enoxaparin Studies (CRETE)
E. Vincent Faustino, MD, MHS - vince.faustino@yale.edu
NCT04924322
Inclusion criteria
• \>36 weeks corrected gestational to \<17 years old
• \<24 hours after insertion of an untunneled CVC
• CVC inserted in the internal jugular or femoral vein Exclusion criteria
• Radiologic diagnosis of CADVT in the site of insertion in prior 6 weeks
• Currently receiving an antithrombotic agent, e.g., LMWH, UFH, warfarin and aspirin, but not UFH at dose to maintain patency of a vascular catheter
• Presence of clinically relevant bleeding, i.e., hemoglobin decreased ≥2 g/dl in 24 hours, required medical or surgical intervention to restore hemostasis, or in the retroperitoneum, pulmonary, intracranial or central nervous system, in the prior 60 days
• Surgery in the prior 7 days
• Major trauma in the prior 7 days
• Presence of coagulopathy, i.e., INR \>2.0, aPTT \>50 seconds or platelet count \<50 x 10\^3/mcL
• Presence of renal failure, i.e., creatinine clearance \<30 mL/min/1.73 m2
• Known hypersensitivity to heparin or pork products
• Laboratory confirmed HIT
• Current pregnancy or lactation
• Presence of an epidural catheter
• Limitation of care
• Previous enrollment in the CRETE Studies
• \>36 weeks corrected gestational to \<17 years old
• \<24 hours after insertion of an untunneled CVC
• CVC inserted in the internal jugular or femoral vein Exclusion criteria
• Radiologic diagnosis of CADVT in the site of insertion in prior 6 weeks
• Currently receiving an antithrombotic agent, e.g., LMWH, UFH, warfarin and aspirin, but not UFH at dose to maintain patency of a vascular catheter
• Presence of clinically relevant bleeding, i.e., hemoglobin decreased ≥2 g/dl in 24 hours, required medical or surgical intervention to restore hemostasis, or in the retroperitoneum, pulmonary, intracranial or central nervous system, in the prior 60 days
• Surgery in the prior 7 days
• Major trauma in the prior 7 days
• Presence of coagulopathy, i.e., INR \>2.0, aPTT \>50 seconds or platelet count \<50 x 10\^3/mcL
• Presence of renal failure, i.e., creatinine clearance \<30 mL/min/1.73 m2
• Known hypersensitivity to heparin or pork products
• Laboratory confirmed HIT
• Current pregnancy or lactation
• Presence of an epidural catheter
• Limitation of care
• Previous enrollment in the CRETE Studies
DRUG: Enoxaparin
Deep Venous Thrombosis
child, critical illness, venous thromboembolism, enoxaparin, thrombin generation, bleed
A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)
ctrrecruit@vcu.edu
NCT04546399
Inclusion Criteria:
* Patients must be \>= 1 and \< 31 years at time of enrollment
* Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories:
* Isolated bone marrow relapse
* Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
* Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes
* Patients with Down syndrome (DS) are eligible in the following categories:
* Isolated bone marrow relapse
* Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression
* Patients must not have had a prior hematopoietic stem cell transplant
* A single intrathecal chemotherapy at the time of relapse will be allowed. If \< 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted
* In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroids and/or hydroxyurea only) is permissible
* Patients with Down syndrome who received pre-enrollment therapy and have a white blood count (WBC) \>= 30,000/ul at the time of enrollment still must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required
* Patients with Down syndrome who received pre-enrollment therapy and have a WBC \< 30,000/ul at the time of enrollment must be given a 24 hour "washout" before starting immunotherapy
* Note: There is no waiting period or "washout" for patients who relapse while receiving upfront therapy
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (within 7 calendar days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male), 0.6 (female)
* 2 to \< 6 years: 0.8 (male), 0.8 (female)
* 6 to \< 10 years: 1 (male), 1 (female)
* 10 to \< 13 years: 1.2 (male), 1.2 (female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients with B-lymphoblastic lymphoma (B-LLy)
* Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
* Patients with Philadelphia chromosome positive (Ph+) B-ALL or ABL class Ph-like B-ALL (i.e. rearrangements involving ABL1, ABL2, CSF1R or PDGFRB and predicted to be sensitive to imatinib or dasatinib)
* Patients with mixed phenotype acute leukemia (MPAL)
* Patients with known Charcot-Marie-Tooth disease
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype
* Patients with active, uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment
* Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection if cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline.
* Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed if blood cultures are negative for \> 48 hours
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Active viral or protozoal infection requiring IV treatment
* Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible.
* Patients with uncontrolled HIV, hepatitis B, or hepatitis C infection. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* Patients with an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Patients with DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible
* Note: Group 3 and 4 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if this is NOT the only site of relapsed disease
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab
* Lactating females are not eligible unless they agree to not breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose RADIATION: 3-Dimensional Conformal Radiation Therapy, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cytarabine, DRUG: Dexamethasone, DRUG: Hydrocortisone Sodium Succinate, PROCEDURE: Lumbar Puncture, DRUG: Mercaptopurine, DRUG: Methotrexate, BIOLOGICAL: Nivolumab, DRUG: Pegaspargase, DRUG: Vincristine Sulfate
Down Syndrome, Recurrent B Acute Lymphoblastic Leukemia
Modeling Mortality in Duchenne Muscular Dystrophy Cardiomyopathy: Identification of Surrogate Outcome Measures for DMD Drug Trials
Jonathan Soslow, MD, MSCI - DMDMachineLearning@vumc.org
NCT07674758
Inclusion Criteria:
* Clinical phenotype of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or muscular dystrophy carrier (MDC) confirmed with muscle biopsy or genotype
Exclusion Criteria:
* Additional genetic or congenital abnormality that may affect cardiovascular function or progression
* Current investigational therapy that may affect cardiovascular function (would preclude ongoing data collection but prior data would still be used) Duchenne Muscular Dystrophy (DMD), Cardiomyopathy, Becker Muscular Dystrophy, Carrier of Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy, cardiomyopathy, machine learning, cardiac MRI, Biomarker, Outcome measures