Revumenib + Chemotherapy for Relapsed/Refractory Leukemia

Recruiting at 78 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Down syndrome, Bone marrow failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like strong CYP3A4 inhibitors or inducers and P-glycoprotein inhibitors or inducers should be avoided during specific parts of the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Research Team

Kelly E Faulk

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for infants and young children aged 1 month to under 6 years, diagnosed with KMT2A-rearranged leukemia that's either relapsed or unresponsive to treatment. They should have a white blood cell count below 50,000/uL and be mostly recovered from previous treatments' side effects. Kids over a year old need to be at least half as active as usual (Lansky Scale >= 50%). Those with severe brain involvement by leukemia must improve before joining.

Inclusion Criteria

My brain and spinal cord are mostly unaffected by leukemia.

I am taking cancer drugs that don't lower my white blood cell count.

White blood cell (WBC) must be < 50,000/uL at the time of study enrollment.

Exclusion Criteria

I have been treated with SNDX-5613 before.

My leukemia is only affecting areas outside of my bone marrow.

Patients diagnosed with Down syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combination Cycle 1

Patients receive revumenib and 3-drug re-induction chemotherapy including vincristine, prednisone, and calaspargase pegol-mknl, along with methotrexate, hydrocortisone, and cytarabine intrathecally.

4 weeks

Weekly visits for chemotherapy administration

Combination Cycle 2

Patients receive revumenib and FLA chemotherapy consisting of fludarabine and high-dose cytarabine.

4 weeks

Weekly visits for chemotherapy administration

Monotherapy

Patients receive revumenib continuously, with optional intrathecal methotrexate, hydrocortisone, and cytarabine as clinically indicated.

Up to 12 cycles of 4 weeks each

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Revumenib

Trial Overview The study tests Revumenib combined with chemotherapy in kids who have specific gene changes in their leukemia cells. The goal is to see if this mix works better than standard treatments alone. It includes drugs like vincristine, prednisone, asparaginase, fludarabine, and cytarabine which stop cancer cells from growing or kill them.

Participant Groups

Group I: Regimen B (revumenib, FLA) Experimental Treatment 10 Interventions

COMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" IV on days 1-5, MTX IT, hydrocortisone IT, and cytarabine IT on day 0 and optionally on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 2 cycles. MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Treatment repeats every 28 days for up to 12 cycles on study in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT on days 0, 8, 15 and 22 as clinically indicated. All patients also undergo ECHO or MUGA, collection of blood and CSF samples, lumbar puncture, and bone marrow aspiration throughout the trial.

Group II: Regimen A (revumenib, 3-drug re-induction, FLA) Experimental Treatment 14 Interventions

See Detailed Description.

Revumenib is already approved in United States for the following indications:

Approved in United States as Revuforj for:

• Relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients aged 1 year and older

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+