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Acute Myeloid LeukemiaPhase 1NCT06313437

Revumenib in Combination With 7+3 + Midostaurin in AML

A Phase 1 study testing Revumenib, Midostaurin and Cytarabine in people with Acute Myeloid Leukemia and AML, Adult, run by Richard Stone, MD at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Revumenib, Midostaurin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
2 sitesUnited States
Study dates
6 Dec 2024to 2 Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 32Show fewer
  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Richard Stone, MD contact

617-632-5157

richard_stone@dfci.harvard.edu

United States2 sites, 2 recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Richard Stone, MD, 617-632-5157, richard_stone@dfci.harvard.edu

    Richard Stone, MD

    Recruiting

  • Yale Cancer Center

    New Haven, Connecticut, 06150

    Maximilian Stahl, MD, maximilian.stahl@yale.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase I Trial of Revumenib in Combination With 7+3 (7 Days of Cytarabine and 3 Days of Daunorubicin) + Midostaurin Induction Chemotherapy for the Frontline Treatment of NPM1 and FLT3 Mutated AML

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)
Read the detailed description

This is a single arm open label phase I trial of the menin inhibitor, revumenib, in combination with cytarabine and daunorubicin (7+3) chemotherapy and the multikinase inhibitor midostaurin for the frontline treatment of Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated Acute Myeloid Leukemia (AML).

Investigators are trying to determine the highest dose of revumenib that can be given safely in combination with these chemotherapy drugs. Treatment consists of 1-2 cycles of so-called "induction treatment" (initial chemotherapy to induce a remission of the leukemia). This "induction treatment" consists of revumenib + 7+3 (7 days of cytarabine + 3 days of daunorubicin) chemotherapy + midostaurin.

The U.S. Food and Drug Administration (FDA) has not approved the combination of revumenib, cytarabine, daunorubicin, and midostaurin as a treatment for AML.

The research study procedures include screening for eligibility, study treatment visits, blood and urine tests, bone marrow biopsies, and electrocardiograms (ECGs).

Participants will receive study treatment as long as there are no serious side effects and the disease does not progress.

The trial will include up to 12 participants in dose finding phase and 10 additional participants in the dose expansion phase for a total participant number of 22 participants.

Syndax Pharmaceuticals is supporting this research study by supply revumenib (SNDX-5613).

Being tested
Revumenib, Midostaurin, Cytarabine, Daunorubicin
Keywords
Acute Myeloid Leukemia, AML, Adult, AML with Gene Mutations, AML, Leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RevumenibDrug

    Also called SNDX-5613, Trans N-ethyl-2-((4-(7-((4-(ethylsulfonamido)cyclohexyl)methyl)-2,7-diazaspiro[3.5]nonan-2- yl)pyrimidin-5-yl)oxy)-5-fluoro-N-isopropylbenzamide

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

  • MidostaurinDrug

    Also called Rydapt

    Kinase inhibitor, capsule taken orally per protocol.

  • CytarabineDrug

    Also called cytosine arabinoside (ara-C)

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

  • DaunorubicinDrug

    Also called Daunomycin

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

Study groups in NCT06313437
Study groupRoleWhat they receive
Dose Escalation RevumenibExperimentalStandard 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
Receives: Drug: Revumenib; Drug: Midostaurin; Drug: Cytarabine; Drug: Daunorubicin
Dose-Expansion RevumenibExperimentalCycles 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
Receives: Drug: Revumenib; Drug: Midostaurin; Drug: Cytarabine; Drug: Daunorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing Dose Limiting Toxicity (DLT)

    Detailed DLT consideration outline in protocol section 5.4.

    Measured: Up to 12 weeks

  2. Maximum Tolerated Dose (MTD)

    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.

    Measured: Up to 12 weeks

  3. Recommended phase II dose (RP2D)

    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.

    Measured: Up to 12 weeks

Secondary outcomes (8)

  1. Complete Remission (CR) rate with induction chemotherapy

    CR rate is defined as the proportion of participants who achieve a CR as defined by the ELN 2022 response criteria after completion of induction chemotherapy.

    Measured: Up to 8 weeks

  2. Complete Remission (CR) rate with consolidation chemotherapy

    CR rate is defined as the proportion of participants who achieve a CR as defined by the ELN 2022 response criteria after completion of consolidation chemotherapy.

    Measured: Up to 12 weeks

  3. Flow Measurable Residual Disease Negative (MRD-) rate with induction chemotherapy

    Flow MRD rate is defined as the proportion of participants who achieve MRD negativity (MRD-) after completion of induction chemotherapy assessed by MRD sensitive flow cytometry.

    Measured: Up to 8 weeks

  4. Flow Measurable Residual Disease Negative (MRD-) rate with consolidation chemotherapy

    Flow MRD rate is defined as the proportion of participants who achieve MRD negativity (MRD-) after completion of consolidation chemotherapy assessed by MRD sensitive flow cytometry.

    Measured: Up to 12 weeks

  5. Molecular Measurable Residual Disease Negative (MRD-) rate with induction chemotherapy

    Molecular MRD rate is defined as the proportion of participants who achieve MRD negativity (MRD-) after completion of induction chemotherapy as assessed by NPM1 MRD testing as well as FLT3 ITD MRD testing and duplex sequencing.

    Measured: Up to 8 weeks

  6. Molecular Measurable Residual Disease Negative (MRD-) rate with consolidation chemotherapy

    Molecular MRD rate is defined as the proportion of participants who achieve MRD negativity (MRD-) after completion of consolidation chemotherapy as assessed by NPM1 MRD testing as well as FLT3 ITD MRD testing and duplex sequencing.

    Measured: Up to 12 weeks

  7. Relapse-Free Survival at 1 year (RFS1)

    RFS is defined as the length of time after the completion of a particular medical treatment during which a patient remains free of any signs or symptoms of disease relapse or recurrence based on Kaplan-Meier methodology.

    Measured: Up to 1 year

  8. Overall Survival at 1 year (OS1)

    OS1 is the probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at the date last known alive.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2024
  2. Study start6 Dec 2024
  3. Primary completion2 Mar 2027 (estimated)
  4. Study completion2 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06313437
Sponsor's protocol ID
24-021
Status last verified
Mar 2026
First submitted
10 Mar 2024
Last updated
25 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Revumenib, Midostaurin and Cytarabine in people with Acute Myeloid Leukemia and AML, Adult, run by Richard Stone, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Richard Stone, MD (617-632-5157, richard_stone@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose Limiting Toxicity (DLT) (time frame: Up to 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06313437.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.

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