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

Eligibility Criteria

Sex

ALL

Age

1 Month - 6 Years

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of blood and CSF samples
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Calaspargase Pegol — DRUG
  Given IV
• Cytarabine — DRUG
  Given IV and IT
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Electrocardiogram — PROCEDURE
  Undergo ECG
• Fludarabine Phosphate — DRUG
  Given IV
• Hydrocortisone Sodium Succinate — DRUG
  Given IT
• Lumbar Puncture — PROCEDURE
  Undergo lumbar puncture
• Methotrexate — DRUG
  Given IT
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA scan
• Prednisolone — DRUG
  Given PO or via NG, NJ, ND or G-tube
• Prednisone — DRUG
  Given PO or via NG, NJ, ND or G-tube
• Revumenib — DRUG
  Given PO or via NG, NJ, ND or G-tube
• Vincristine Sulfate — DRUG
  Given IV

Study Details

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.

Key Dates

Start date

Jan 8, 2024

Status verified

Apr 2026

Primary completion

Dec 31, 2027

Completion

Dec 31, 2027

Study Design

Enrollment

78 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Regimen A (revumenib, 3-drug re-induction, FLA)
  See Detailed Description.
• Experimental: Regimen B (revumenib, FLA)
  COMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" consisting of fludarabine IV and high-dose cytarabine IV on days 1-5, and MTX IT, hydrocortisone IT, and cytarabine IT on day 0 then optionally on days 8, 15, and 22. Cycles are a minimum of 29 days in duration. MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT. All patients also undergo ECHO or MUGA, ECG, collection of blood, CSF and bone marrow samples, lumbar puncture, and bone marrow aspiration throughout the trial.

Primary Outcome Measure

Incidence of dose-limiting toxicities (DLTs) for lymphoid directed chemotherapy block (Safety Phase) [ Time Frame: At the end of Cycle 1 of Regimen A (each cycle is a minimum of 29 days) ]

Locations (75)

Find similar trials in Birmingham, AL

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