protocolSection identificationModule nctId: NCT06317662, orgStudyIdInfo id: NCI-2024-01994, secondaryIdInfos id: NCI-2024-01994, type: REGISTRY, domain: CTRP (Clinical Trial Reporting Program), secondaryIdInfos id: AALL2321, type: OTHER, domain: Children's Oncology Group, secondaryIdInfos id: AALL2321, type: OTHER, domain: CTEP, secondaryIdInfos id: U10CA180886, type: NIH, link: https://reporter.nih.gov/quickSearch/U10CA180886, briefTitle: 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, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-07-31, primaryCompletionDateStruct date: 2027-12-21, completionDateStruct date: 2027-12-21, studyFirstPostDateStruct date: 2024-03-19, lastUpdatePostDateStruct date: 2024-04-25, sponsorCollaboratorsModule leadSponsor name: National Cancer Institute (NCI), class: NIH, descriptionModule briefSummary: This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL., conditionsModule conditions: Acute Leukemia of Ambiguous Lineage, conditions: B Acute Lymphoblastic Leukemia, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: SEQUENTIAL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 171, type: ESTIMATED, armsInterventionsModule interventions name: Asparaginase Erwinia chrysanthemi, interventions name: Biospecimen Collection, interventions name: Blinatumomab, interventions name: Bone Marrow Aspiration, interventions name: Calaspargase Pegol, interventions name: Computed Tomography, interventions name: Cyclophosphamide, interventions name: Cytarabine, interventions name: Daunorubicin, interventions name: Dexamethasone, interventions name: Doxorubicin, interventions name: Echocardiography, interventions name: FDG-Positron Emission Tomography, interventions name: Leucovorin, interventions name: Lumbar Puncture, interventions name: Magnetic Resonance Imaging, interventions name: Mercaptopurine, interventions name: Methotrexate, interventions name: Multigated Acquisition Scan, interventions name: Pegaspargase, interventions name: Prednisolone, interventions name: Prednisone, interventions name: Therapeutic Hydrocortisone, interventions name: Thioguanine, interventions name: Venetoclax, interventions name: Vincristine, outcomesModule primaryOutcomes measure: Incidence of dose-limiting toxicities (DLTs) (safety phase), primaryOutcomes measure: Incidence of DLTs (expansion phase), primaryOutcomes measure: Minimal residual disease (MRD)-negative remission rate, secondaryOutcomes measure: Event free survival (EFS) rates of infants with KMT2A-R acute lymphoblastic leukemia (ALL), secondaryOutcomes measure: 3-year EFS of infants with KMT2A-R ALL, secondaryOutcomes measure: Proportion of KMT2A-G patients in Arm C who are able to receive all treatment cycles before maintenance, secondaryOutcomes measure: Pharmacokinetics (PK) of venetoclax in infants, otherOutcomes measure: 3-year EFS of infants with KMT2A-R ALL treated on Arm B, otherOutcomes measure: 3-year EFS of infants with KMT2A-G ALL treated on Arm C, otherOutcomes measure: Use of high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized flow cytometry, otherOutcomes measure: PK of calaspargase pegol in infants with ALL, otherOutcomes measure: Incidence of CD19-negative relapse and myeloid switch relapse with protocol therapy, otherOutcomes measure: Impact of venetoclax in combination with chemotherapy on T-cell subsets and function, otherOutcomes measure: Feasibility of T-cell collection and success of T-cell manufacturing for infants with KMT2A-R ALL who receive chimeric antigen receptor T-cell therapy, otherOutcomes measure: Predictors of response and resistance to venetoclax and overall protocol therapy, otherOutcomes measure: Impact of subsequent anti-cancer therapy on overall survival, eligibilityModule sex: ALL, maximumAge: 365 Days, stdAges: CHILD, contactsLocationsModule, hasResults: False