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

Conditions

• Acute Leukemia of Ambiguous Lineage
• B Acute Lymphoblastic Leukemia

Eligibility Criteria

Sex

ALL

Age

N/A - 365 Days

Healthy Volunteers

Not accepted

Interventions

• Asparaginase Erwinia chrysanthemi — DRUG
  Given recombinant crisantaspase IM or crisantaspase IM or IV
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Blinatumomab — BIOLOGICAL
  Given IV
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Calaspargase Pegol — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT
• Cyclophosphamide — DRUG
  Given IV
• Cytarabine — DRUG
  Given IT or IV
• Daunorubicin — DRUG
  Given IV
• Dexamethasone — DRUG
  Given PO or NG or IV
• Doxorubicin — DRUG
  Given IV
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• FDG-Positron Emission Tomography — PROCEDURE
  Undergo FDG-PET
• Leucovorin — DRUG
  Given PO or NG or IV
• Levoleucovorin — DRUG
  Given IV
• Lumbar Puncture — PROCEDURE
  Undergo lumbar puncture
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Mercaptopurine — DRUG
  Given PO or NG
• Methotrexate — DRUG
  Given IT or IV or PO or NG
• Methylprednisolone — DRUG
  Given IV
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Prednisolone — DRUG
  Given PO or NG
• Prednisone — DRUG
  Given PO or NG
• Therapeutic Hydrocortisone — DRUG
  Given IT
• Thioguanine — DRUG
  Given PO or NG
• Venetoclax — DRUG
  Given PO or NG
• Vincristine — DRUG
  Given IV

Study Details

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.

Key Dates

Start date

Jun 5, 2025

Status verified

Jan 2026

Primary completion

Dec 31, 2028

Completion

Dec 31, 2028

Study Design

Enrollment

153 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A
  See Detailed Description for Arm A.
• Experimental: Arm B, Cohort 1
  See Detailed Description for Arm B, Cohort 1.
• Experimental: Arm B, Cohort 2
  See Detailed Description for Arm B, Cohort 2.
• Experimental: Arm B, Cohort 3
  See Detailed Description for Arm B, Cohort 3.
• Experimental: Arm B, Cohort 4
  See Detailed Description for Arm B, Cohort 4.
• Experimental: Arm C
  See Detailed Description for Arm C.
• Experimental: Safety Phase Cohort
  See Detailed Description for Safety Phase Cohort.
• Experimental: Steroid Prephase(prednisone, prednisolone, methylprednisolone)
  All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).

Primary Outcome Measure

Incidence of dose-limiting toxicities (DLTs) (safety phase) [ Time Frame: For the duration of the induction + venetoclax cycle ]

Locations (112)

Find similar trials in Birmingham, AL

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