~15 spots leftby Mar 2026

Revumenib + Standard Treatments for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)
+1 other location
RS
Overseen byRichard Stone, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Maximilian Stahl, MD
Must be taking: Menin inhibitors
Must not be taking: CYP3A4 inducers, QTc prolonging
Disqualifiers: CNS involvement, HIV, Hepatitis, others
No Placebo Group
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This research is being conducted to determine a safe and effective dose of revumenib that can be given in combination with standard induction (initial therapy to induce a remission) + FLT3 targeted therapy (midostaurin) and a single cycle of post-remission therapy + FLT3 targeted therapy (midostaurin) to participants with newly diagnosed Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated Acute Myeloid Leukemia (AML). The names of the study drugs involved in this study are: * Revumenib (SNDX-5613) (a type of menin inhibitor) * Midostaurin (a type of multi-kinase including FLT3 inhibitor) * Cytarabine (a type of antineoplastic agent) * Daunorubicin (a type of antineoplastic agent)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken strong CYP3A4 inducers within 7 days before starting the study. Also, drugs that prolong QTc should be avoided if possible.

What data supports the effectiveness of the drug combination Revumenib + Standard Treatments for Acute Myeloid Leukemia?

Research shows that about 50% to 75% of adults with acute myeloid leukemia achieve complete remission with cytarabine and an anthracycline like daunorubicin, which are part of the standard treatments. Additionally, new targeted agents like FLT3 inhibitors, which include midostaurin, have shown promise in improving outcomes for patients with specific genetic abnormalities.12345

Is the combination of Revumenib and standard treatments for Acute Myeloid Leukemia safe?

The combination of daunorubicin and cytarabine, used in treatments like Vyxeos, has been approved for certain types of Acute Myeloid Leukemia and has a known safety profile. Common side effects include rash, fever, fatigue, and low blood cell counts, which are similar to those seen with standard treatments. Always consult with a healthcare provider for personalized advice.13678

What makes the drug combination of Revumenib, Cytarabine, Daunorubicin, and Midostaurin unique for treating acute myeloid leukemia?

This drug combination is unique because it includes Revumenib, a novel agent, alongside standard chemotherapy drugs Cytarabine and Daunorubicin, and the FLT3 inhibitor Midostaurin, which targets specific genetic mutations in acute myeloid leukemia, potentially offering a more tailored and effective treatment approach.39101112

Research Team

RS

Richard Stone, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for people newly diagnosed with a specific type of blood cancer called Acute Myeloid Leukemia (AML) that has certain genetic changes (NPM1 and FLT3 mutations). Participants should be starting their first treatment.

Inclusion Criteria

aspartate aminotransferase (AST) ≤ 2.5 × ULN*
Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)
My side effects from previous treatments are mild.
See 29 more

Exclusion Criteria

I have hepatitis B or C, but my viral load has been undetectable in the last 3 months.
Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
My heart condition limits my physical activity but I can still perform light tasks.
See 11 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Induction Treatment

Participants receive induction chemotherapy with revumenib, cytarabine, daunorubicin, and midostaurin to induce remission

4 weeks
Daily visits during treatment days

Reinduction Cycle

Participants may receive a second cycle of induction therapy if needed

4 weeks
Daily visits during treatment days

Consolidation Cycle

Participants receive consolidation chemotherapy to maintain remission

4 weeks
Daily visits during treatment days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks
Regular follow-up visits

Treatment Details

Interventions

  • Cytarabine (Antineoplastic Agent)
  • Daunorubicin (Antineoplastic Agent)
  • Midostaurin (FLT3 Inhibitor)
  • Revumenib (Menin Inhibitor)
Trial OverviewThe study is testing the safety and effectiveness of a new drug, Revumenib, when used with standard AML treatments Midostaurin, Cytarabine, and Daunorubicin. The goal is to find the best dose of Revumenib in this combination.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Dose-Expansion RevumenibExperimental Treatment4 Interventions
Cycles are 28 days * Baseline visit and assessments * Induction Cycle: * Days 1-3: Predetermined dose of Daunorubicin 1x daily * Days 1-7: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Induction visit * Follow-up * Reinduction Cycle: Therapy will be administered in the hospital * Days 1-2: Predetermined dose of Daunorubicin 1x daily * Days 1-5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Reinduction visit * Follow-up * Consolidation Cycle: Therapy will be administered in the hospital * Days 1, 3, and 5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Consolidation visit * Follow up
Group II: Dose Escalation RevumenibExperimental Treatment4 Interventions
Standard 3+3 design for a recommended phase 2 dose of Revumenib per dose-limiting toxicity rules. Cycles are 28 days. * Baseline * Induction Cycle: * Days 1-3: Predetermined dose of Daunorubicin 1x daily * Days 1-7: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Induction visit * Follow-up * Reinduction Cycle: Therapy will be administered in the hospital * Days 1-2: Predetermined dose of Daunorubicin 1x daily * Days 1-5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of reinduction visit * Follow-up * Consolidation Cycle: Therapy will be administered in the hospital * Days 1, 3, and 5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of consolidation visit * Follow up

Cytarabine is already approved in Canada for the following indications:

🇨🇦
Approved in Canada as Cytosar-U for:
  • Acute myeloid leukemia
  • Acute lymphocytic leukemia
  • Chronic myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Maximilian Stahl, MD

Lead Sponsor

Trials
2
Recruited
130+

Richard Stone, MD

Lead Sponsor

Trials
2
Recruited
50+

Syndax Pharmaceuticals

Industry Sponsor

Trials
49
Recruited
2,700+

Findings from Research

In a study of 155 patients with relapsed or refractory acute myeloid leukemia, the Ara-C couplets regimen showed a higher overall response rate (54.4%) compared to the MEC regimen (43.7%), although this difference was not statistically significant (P = 0.10).
Patients receiving Ara-C couplets had significantly better outcomes in terms of overall survival and progression-free survival, were more likely to proceed to allogeneic stem cell transplant (54.4% vs 31%; P = 0.003), and experienced fewer severe toxicities, such as febrile neutropenia and gastrointestinal issues, indicating a safer profile for Ara-C couplets.
A multi-institutional comparison of mitoxantrone, etoposide, and cytarabine vs high-dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia.Christian, S., Arain, S., Patel, P., et al.[2022]
Younger adults with acute myeloid leukemia (AML) have seen better treatment outcomes over the past 40 years, but older adults have not experienced similar improvements, with only 20% to 30% achieving long-term survival after initial treatment.
Recent advances in understanding AML's molecular mechanisms have led to the development of targeted therapies, such as FLT3 inhibitors and immunoconjugates, which represent a promising new direction for treatment.
Drug therapy for acute myeloid leukemia.Tallman, MS., Gilliland, DG., Rowe, JM.[2022]
Acute myeloid leukemia (AML) treatment has seen little change in 40 years, but new agents like IDH inhibitors and antibody-drug conjugates show promise in improving outcomes, either alone or with traditional chemotherapy.
A variety of novel therapies, including cytotoxic agents, epigenetic modifiers, and targeted inhibitors, are currently being tested in clinical trials, indicating a potential shift in AML management strategies.
Emerging therapies for acute myeloid leukemia.Saygin, C., Carraway, HE.[2023]

References

A multi-institutional comparison of mitoxantrone, etoposide, and cytarabine vs high-dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia. [2022]
Drug therapy for acute myeloid leukemia. [2022]
Emerging therapies for acute myeloid leukemia. [2023]
Therapeutic Advances in First-Line Management of Acute Myeloid Leukemia. [2020]
Cellular and pharmacologic aspects of drug resistance in acute myeloid leukemia. [2019]
FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. [2020]
EMA Review of Daunorubicin and Cytarabine Encapsulated in Liposomes (Vyxeos, CPX-351) for the Treatment of Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes. [2022]
Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD. [2023]
Midostaurin in Combination With Standard Chemotherapy for Treatment of Newly Diagnosed FMS-Like Tyrosine Kinase 3 (FLT3) Mutation-Positive Acute Myeloid Leukemia. [2019]
Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. [2020]
11.United Statespubmed.ncbi.nlm.nih.gov
The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin. [2020]
Chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CDCAG) in patients with relapsed/refractory acute myeloid leukemia: a single-arm, phase 1/2 study. [2021]