Revumenib for Acute Leukemia

Overseen By Brian Ball, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: CYP3A4 inhibitors

Must not be taking: QT prolonging medications

Disqualifiers: Acute promyelocytic leukemia, HIV, Hepatitis B/C, others

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

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 2 years

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new drug, revumenib, for individuals with acute leukemia who have undergone a stem cell transplant. Revumenib blocks certain proteins that aid leukemia cell growth. The trial aims to determine if revumenib can safely prevent leukemia from returning or growing. Suitable candidates for this trial have had a stem cell transplant in the last few months and are in remission from leukemia. As a Phase 1 trial, this research focuses on understanding how revumenib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be able to take a strong CYP3A4 inhibiting antifungal at least 7 days before starting revumenib, and you cannot use medications known to prolong the QT interval, except for certain low-risk drugs used as standard supportive therapies.

Is there any evidence suggesting that revumenib is likely to be safe for humans?

Research has shown that revumenib is generally safe for patients with acute leukemia. In earlier studies, the side effects of revumenib were expected and manageable. The FDA approved revumenib for a specific type of acute leukemia, indicating confidence in its safety. The main side effects in these studies aligned with expectations for this kind of treatment. This information should reassure participants considering joining the trial about the safety of revumenib. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute leukemia, which often involve chemotherapy or targeted therapies like tyrosine kinase inhibitors, Revumenib has researchers excited because it targets a unique pathway. Revumenib works by inhibiting the menin-MLL interaction, a mechanism that is crucial for the survival of certain leukemia cells. This targeted approach has the potential to be more effective for patients with specific genetic mutations, offering a new line of attack against the cancer. Additionally, Revumenib is taken orally, which can be more convenient compared to intravenous treatments.

What evidence suggests that revumenib might be an effective treatment for acute leukemia?

Research has shown that revumenib, which participants in this trial will receive, may help treat acute leukemia. In clinical trials, about 21% of patients experienced complete remission, where all signs of cancer disappeared, or partial recovery. Revumenib helped some patients reduce or eliminate leukemia signs, at least temporarily. The treatment blocks a protein interaction that aids leukemia cell growth. By stopping this interaction, revumenib may prevent leukemia cells from surviving and multiplying. These findings suggest that revumenib could be effective for people with acute leukemia, especially after a stem cell transplant. ^{3 5 6 7 8}

Who Is on the Research Team?

Brian Ball, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with acute leukemia who have undergone an allogeneic stem cell transplant. It's designed to test the safety and effectiveness of a new medication called revumenib, which targets proteins that help leukemia cells grow.

Inclusion Criteria

Any donor or graft source will be included

I am a woman who can have children, not pregnant, and agree to use birth control.

I have been treated with menin inhibitors before my stem cell transplant.

Exclusion Criteria

I have not had a stem cell transplant for acute promyelocytic leukemia.

I can take strong CYP3A4 inhibitors and do not need medications that prolong the QT interval.

History of or concurrent conditions that may confound study results or interfere with participation are exclusion criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive revumenib orally once daily or every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years.

Up to 2 years

Regular visits for bone marrow aspiration and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months for up to 2 years.

Up to 2 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Revumenib

Trial Overview The study involves testing revumenib, a menin inhibitor drug, to determine its best dose and how well it can treat acute leukemia post-transplant. The trial includes various assessments like bone marrow tests, heart scans (echocardiography), and health questionnaires.

How Is the Trial Designed?

Group I: Treatment (revumenib) Experimental Treatment 8 Interventions

Starting 50-150 days after alloHCT, patients receive revumenib PO QD or every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy during screening and may undergo ECHO during screening and as clinically indicated. Patients also undergo bone marrow aspiration and collection of blood samples throughout the trial.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. 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 ...

2. revuforj.com revuforj.com/trial-results/

Trial Results | Revuforj® (revumenib) Official Patient Site In the clinical trial, 21% of people (22 out of 104) achieved complete remission (CR) or complete remission with a partial hematologic recovery (CRh).

3. 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 ...

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00826

Menin Inhibition With Revumenib for KMT2A-Rearranged ... Treatment with revumenib resulted in rates of complete remission (CR) or CR with partial hematologic recovery (CR +CRh) that exceeded the null ...

6. 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 safety evaluation of Revuforj was based on the FDA's analysis of 241 patients (207 adult and 34 pediatric patients) with R/R acute leukemia ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40332046/

Menin inhibition with revumenib for NPM1-mutated ... The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as ...

8. ashpublications.org ashpublications.org/blood/article/146/9/1065/537139/Menin-inhibition-with-revumenib-for-NPM1-mutated

Menin inhibition with revumenib for NPM1-mutated relapsed ... The safety profile of revumenib in R/R NPM1m AML was consistent with that found in other acute leukemias and was predictable, with AEs primarily related to ...