Revumenib in Combination With 7+3 + Midostaurin in AML

Recruiting now · Phase 1

Conditions studied: Acute Myeloid Leukemia, AML, Adult, AML With Gene Mutations, AML, Leukemia

In brief

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)

Key facts

Study ID

NCT06313437

Run by

Richard Stone, MD

People needed

22

Starts

2024-12-06

Expected to finish

2028-03-02

Last updated by the study team

2026-03-25

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

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