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

Summary

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.

Conditions

• Acute Leukemia of Ambiguous Lineage
• B Acute Lymphoblastic Leukemia

Interventions

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

FDG-Positron Emission Tomography

Undergo FDG-PET

DRUG

Leucovorin

Given PO or NG or IV

DRUG

Levoleucovorin

Given IV

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Mercaptopurine

Given PO or NG

DRUG

Methotrexate

Given IT or IV or PO or NG

DRUG

Methylprednisolone

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

DRUG

Prednisolone

Given PO or NG

DRUG

Prednisone

Given PO or NG

DRUG

Therapeutic Hydrocortisone

Given IT

DRUG

Thioguanine

Given PO or NG

DRUG

Venetoclax

Given PO or NG

DRUG

Vincristine

Given IV

DRUG

Asparaginase Erwinia chrysanthemi

Given recombinant crisantaspase IM or crisantaspase IM or IV

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

BIOLOGICAL

Blinatumomab

Given IV

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

DRUG

Calaspargase Pegol

Given IV

PROCEDURE

Computed Tomography

Undergo CT

DRUG

Cyclophosphamide

Given IV

DRUG

Cytarabine

Given IT or IV

DRUG

Daunorubicin

Given IV

DRUG

Dexamethasone

Given PO or NG or IV

DRUG

Doxorubicin

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Erin H Breese · Children's Oncology Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Max Age

365 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-05

Primary Completion

2028-12-31

Completion

2028-12-31

FDA Drug

Yes

Countries

• United States
• Puerto Rico

Study Locations