A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia

Summary

This phase II trial tests the safety and best dose of revumenib in combination with chemotherapy, and evaluates whether this treatment improves the outcome in infants and young children who have leukemia that has come back (relapsed) or does not respond to treatment (refractory) and is associated with a KMT2A (MLL) gene rearrangement (KMT2A-R). Leukemia is a cancer of the white blood cells, where too many underdeveloped (abnormal) white blood cells, called "blasts", are found in the bone marrow, which is the soft, spongy center of the bones that produces the three major blood cells: white blood cells to fight infection; red blood cells that carry oxygen; and platelets that help blood clot and stop bleeding. The blasts crowd out the normal blood cells in the bone marrow and spread to the blood. They can also spread to the brain, spinal cord, and/or other organs of the body. The leukemia cells of some children have a genetic change in which a gene (KMT2A) is broken and combined with other genes that typically do not interact with one another; this is called "rearranged". This genetic rearrangement alters how other genes are turned on or off in the cell, turning on genes that drive the development of leukemia. Patients with KMT2A rearrangement have higher risk for cancer coming back after treatment. Revumenib is an oral medicine that directly targets the changes that occur in a cell with a KMT2A rearrangement and has been shown to specifically kill these leukemia cells in preclinical laboratory settings and in animals. Drugs used in chemotherapy, such as vincristine, prednisone, asparaginase, fludarabine and cytarabine 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. This trial is being done to find out if the combination of revumenib and chemotherapy would be safe and/or effective in treating infants and young children with relapsed or refractory KMT2A-R leukemia.

Conditions

• Recurrent Acute Leukemia of Ambiguous Lineage
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage
• Recurrent Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged
• Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia
• Recurrent Mixed Phenotype Acute Leukemia
• Refractory Acute Leukemia of Ambiguous Lineage
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage
• Refractory Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged
• Refractory Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia
• Refractory Mixed Phenotype Acute Leukemia

Interventions

PROCEDURE

Biospecimen Collection

Undergo collection of blood and CSF samples

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

DRUG

Calaspargase Pegol

Given IV

DRUG

Cytarabine

Given IV and IT

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

Electrocardiogram

Undergo ECG

DRUG

Fludarabine Phosphate

Given IV

DRUG

Hydrocortisone Sodium Succinate

Given IT

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

DRUG

Methotrexate

Given IT

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA scan

DRUG

Prednisolone

Given PO or via NG, NJ, ND or G-tube

DRUG

Prednisone

Given PO or via NG, NJ, ND or G-tube

DRUG

Revumenib

Given PO or via NG, NJ, ND or G-tube

DRUG

Vincristine Sulfate

Given IV

Sponsors & Collaborators

• Children's Oncology Group

  lead NETWORK

Principal Investigators

• Kelly E Faulk · Children's Oncology Group

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Month

Max Age

6 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-08

Primary Completion

2027-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States
• Canada

Study Locations