Revumenib + Chemotherapy for Relapsed/Refractory Leukemia

Not currently recruiting at 88 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the safety of revumenib, a new oral medicine, when combined with chemotherapy to treat young children whose leukemia has returned or does not respond to treatment. It specifically targets leukemia with a KMT2A (MLL) gene rearrangement, a genetic change that makes the cancer more difficult to treat. The trial includes two groups: one taking revumenib alone and the other combining it with chemotherapy drugs. Children diagnosed with leukemia before age two who now face a relapse or resistant form of leukemia may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering hope for effective treatment options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that revumenib has been tested and approved by the FDA for treating certain types of leukemia. In earlier studies, 25% of patients experienced differentiation syndrome, a reaction related to the drug's effect on leukemia cells. Most cases were mild, with severe cases being less common. This syndrome typically occurs when leukemia cells begin maturing quickly, indicating the drug's effectiveness. The drug is generally well-tolerated, and serious side effects are rare. This suggests revumenib can be a safe option, especially since it is already approved for similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Revumenib is unique because it targets specific proteins involved in the development of leukemia, offering a new approach compared to traditional chemotherapy options like cytarabine and daunorubicin, which broadly attack rapidly dividing cells. Researchers are excited about revumenib because it can be given orally or through various feeding tubes, providing more flexibility and potentially fewer side effects than intravenous chemotherapy. Additionally, revumenib's targeted mechanism may result in more effective treatment for relapsed or refractory leukemia, especially for patients who haven’t responded well to conventional therapies.

What evidence suggests that the combination of revumenib and chemotherapy could be effective for relapsed or refractory KMT2A-R leukemia?

Research has shown that revumenib yields promising results for treating leukemia that is recurrent or difficult to treat, particularly in patients with genetic changes like the KMT2A rearrangement. In studies, about 23% of patients achieved complete remission, with no signs of cancer, or a partial recovery of blood counts. The overall response rate, including these remissions, was nearly 48%. In this trial, participants will receive revumenib in different regimens. Revumenib targets changes in leukemia cells, helping to kill them and reduce the disease, making it a hopeful option for those with difficult-to-treat leukemia. ^{1 2 3 4 5}

Who Is on the Research Team?

Kelly E Faulk

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

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

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

Exclusion Criteria

Patients diagnosed with Down syndrome.

I have been treated with SNDX-5613 before.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation

FDA approves revumenib for relapsed or refractory acute ... The main efficacy outcome measures were complete remission rate (CR), CR with partial hematological recovery (CRh), CR+CRh duration, and ...

2. ir.syndax.com ir.syndax.com/news-releases/news-release-details/syndax-announces-compelling-revuforjr-revumenib-and-niktimvotm

Syndax Announces Compelling Revuforj® (revumenib) and ... In clinical trials, DS occurred in 60 (25%) of 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute ...

3. ir.syndax.com ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-approval-revuforjr-revumenib-adult-and

Syndax Announces FDA Approval of Revuforj® (revumenib) in ... The rate of complete remission (CR) plus CR with partial hematological recovery (CRh) was 23% (15/65 pts; 95% CI: 14%, 35%). The median time to ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40437770/

Revumenib for Relapsed or Refractory Acute Leukemia ... Differentiation syndrome, related to revumenib's antileukemic effect, was observed in 29% of patients (grade 3/4: 13%; grade 5: <1%). We also ...

5. onclive.com onclive.com/view/fda-approves-revumenib-for-relapsed-refractory-npm1-mutant-acute-myeloid-leukemia

FDA Approves Revumenib for Relapsed/Refractory NPM1- ... The CRc rate reached 32.5% (95% CI, 22.2%-44.1%), and the ORR was 48.1%. Best responses included CR (20.8%), CRh (5.2%), CR with incomplete ...