Recruiting

Phase 1

Revumenib & MidostaurinRevumenib in Combination With 7+3 + Midostaurin in AML

Sponsor:

Richard Stone, MD

Code:

NCT06313437

Conditions

Acute Myeloid Leukemia

AML, Adult

AML With Gene Mutations

AML

Leukemia

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Revumenib

Midostaurin

Cytarabine

Daunorubicin

Study Details

Brief summary:

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)

Conditions

Acute Myeloid Leukemia

AML, Adult

AML With Gene Mutations

AML

Leukemia

Study ID

NCT06313437

Start date

Dec 6, 2024

Status verified date

Mar, 2026

Completion date

Mar 2, 2028

Anticipated

Primary completion date

Mar 2, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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 Criteria:

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.

Study Design

Enrollment

22 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation Revumenib

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

experimental: Dose-Expansion Revumenib

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

Interventions

Revumenib

Menin inhibitor, 25 and 113 mg capsules, taken orally per protocol.

Midostaurin

Kinase inhibitor, capsule taken orally per protocol.

Cytarabine

Antineoplastic agent, via intravenous (into the vein) infusion per protocol.

Daunorubicin

Antineoplastic agent, via intravenous (into the vein) infusion per protocol.

Primary outcome measure

Number of Participants Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Up to 12 weeks ]
Maximum Tolerated Dose (MTD) [ Time Frame: Up to 12 weeks ]
Recommended phase II dose (RP2D) [ Time Frame: Up to 12 weeks ]

Central Contacts and Locations

Central contacts

Richard Stone, MD

617-632-5157 richard_stone@dfci.harvard.edu

Locations

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06150

Contacts

Maximilian Stahl, MD

maximilian.stahl@yale.edu

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Richard Stone, MD

617-632-5157 richard_stone@dfci.harvard.edu

Principal Investigator:

Richard Stone, MD

More Information

Sponsor

Richard Stone, MD

Last update posted

Mar 25, 2026

Last verified

Mar, 2026

Keywords

Acute Myeloid Leukemia
AML, Adult
AML with Gene Mutations
AML
Leukemia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Richard Stone, MD on 2026-03-25.