Revumenib with Chemotherapy and Midostaurin for Newly Diagnosed AML
This study is testing a new combination of medicines for adults (ages 18-75) with newly diagnosed Acute Myeloid Leukemia (AML) that has specific gene mutations (NPM1 and FLT3). Researchers want to find a safe and effective dose of revumenib, a menin inhibitor, when given with standard chemotherapy (cytarabine and daunorubicin) and midostaurin, a targeted therapy. The goal is to see how many participants experience side effects and to determine the best dose for future studies. You may be eligible if you have newly diagnosed AML with these specific gene mutations and meet other criteria. The study plans to enroll 22 participants. The combination of these drugs is not yet approved by the FDA for AML.
- Study design
- This is a single-arm, open-label study, meaning all participants receive the same treatment, and everyone knows what treatments are being given. It aims to enroll up to 22 participants to find the safest and most effective dose.
- What's involved
- You would undergo screening, receive study treatment, and have blood and urine tests, bone marrow biopsies, and electrocardiograms (ECGs). Treatment continues as long as there are no serious side effects and your disease does not worsen.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary goals for safety and dose finding are measured for up to 12 weeks.
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NCT06313437
Revumenib in Combination With 7+3 + Midostaurin in AML
Recruiting
PHASE1Ages 18–75InterventionalTreatmentRichard Stone, MDInvestigator-initiated
~22 participants
Updated 2026-03-25 on ClinicalTrials.gov
What's tested:RevumenibMidostaurinCytarabineDaunorubicin
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Number of Participants Experiencing Dose Limiting Toxicity (DLT)
Measured over Up to 12 weeks
+2 more outcomes measured
Conditions
Where it's being run
2 sites across 2 statesConnecticut1
Massachusetts1
Study leadership
- Richard Stone, MD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Patients with AML who are newly diagnosed according to the WHO 2022 Classification and previously untreated except for hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant).
Patients must be ≥ 18 and \< 75 years old.
Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
Presence of FLT3-ITD and/or TKD mutation(s) AND NPM1 mutation in bone marrow or peripheral blood
Dose escalation phase only: Presence of any of the following adverse risk genetic characteristics:
2022 ELN adverse risk genetic features:
t(6;9)(p23.3;q34.1)/DEK::NUP214
t(v;11q23.3)/KMT2A-rearranged
t(9;22)(q34.1;q11.2)/BCR::ABL1
t(8;16)(p11.2;p13.3)/KAT6A::CREBBP
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1)
t(3q26.2;v)/MECOM(EVI1)-rearranged
-5 or del(5q); -7; -17/abn(17p)
Complex karyotype, monosomal karyotype
Mutations in either one of these genes: ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
Mutated TP53
NPM1 + FLT3-ITD + DNMT3A mutation
LVEF ≥ 50% by MUGA or ECHO at screening.
Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min; determined by the Cockcroft Gault formula.
Adequate liver function as demonstrated by:
aspartate aminotransferase (AST) ≤ 2.5 × ULN\*
alanine aminotransferase (ALT) ≤ 2.5× ULN\*
total bilirubin ≤ 1.5 × ULN\* \* Unless considered due to leukemic organ involvement. Note: Subjects with Gilbert's Syndrome may have a total bilirubin \> 1.5 × ULN per discussion with the Sponsor-Investigator
Resolution of adverse reactions to prior drug therapy (such as hydroxyurea) to ≤ grade 1
Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy based on the opinion of the treating physician.
Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum or urine pregnancy test performed within 7 days of day 1.
Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)
Consolidation should occur between 1-4 weeks following count recovery after induction and remission (must be confirmed by labs to document maximal response) is established. Subjects will receive medium intensity cytarabine -based consolidation in combination with midostaurin and revumenib if the following criteria are fulfilled.
an induction response \< 5% blasts in the bone marrow and ANC \>1000 and PLT \>75000 for whom documented path report is submitted.
sufficiently fit (performance status \<3)
resolution of any adverse reactions to no greater than grade 1 severity
Exclusion
Subject has acute promyelocytic leukemia, inversion (16), t(8;21) AML as described below. Contact Sponsor-Investigator with questions. Inversion 16 and t(8;21): CBF chromosomal abnormalities may be assessed by molecular (PCR), metaphase cytogenetics, or FISH.
Subject has known active CNS involvement with AML.
Subject has received a strong CYP3A4 inducer (APPENDIX C) within 7 days prior to the initiation of study treatment
Strong CYP3A4 inhibitors (APPENDIX C) are contraindicated except strong CYP3A4 inhibitor antifungal azole medications (systemic itraconazole, ketoconazole, posaconazole, voriconazole). For strong CYP3A4 inhibitor antifungal azole medications, the starting dose of revumenib has to be adjusted (Table 1).
QTc using Fridericia's correction \[QTcF\]) \> 450 msec. Drugs that prolong QTc should be avoided if possible. A list of common QTc prolonging drugs and alternatives that are not QTc prolonging can be found in APPENDIX D.
Subject has tested positive for HIV (due to potential drug-drug interaction between antiretroviral medications and Midostaurin/revumenib). Note: HIV testing is not required.
Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and antiHBs+\] are allowed.
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.
Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
Subject has chronic respiratory disease that requires continuous oxygen use.
Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled systemic infection.
Subject has a history of other malignancies prior to study entry, with the exception of:
Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
Prior malignancies treated with (surgery+/- chemotherapy+/- radiation) that have remained disease free for at least two years after completion of therapy
Subject treated with any form of chemotherapy, immunotherapy, or investigative agent within 1 month of enrollment.
Patients who have had prior exposure to a menin inhibitor.
What this trial measures
- Number of Participants Experiencing Dose Limiting Toxicity (DLT)Up to 12 weeks
Detailed DLT consideration outline in protocol section 5.4.
- Maximum Tolerated Dose (MTD)Up to 12 weeks
MTD is determined by the number of patients who experience a DLT. See previous primary outcome measure for the DLT definition. If 0 out of 3 participants experience DLT, next dose level will be proceeded. If \>=1 out of the group suffer DLT, dose escalation will be stopped and 3 additional participants will be entered at the next lowest dose level. If \<=1 out of 6 DLTs, this dose level is considered as MTD.
- Recommended phase II dose (RP2D)Up to 12 weeks
The RP2D is determined by a combination of the MTD (see previous primary outcome measure), pharmacokinetics, pharmacodynamics and response rate to different doses of revumenib in combination with chemotherapy and the FLT3 inhibitor midostaurin.