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
Richard Stone, MD
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)
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 "induct…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
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 bo…
Interventions
- DrugRevumenib
Menin inhibitor, 25 and 113 mg capsules, taken orally per protocol.
- DrugMidostaurin
Kinase inhibitor, capsule taken orally per protocol.
- DrugCytarabine
Antineoplastic agent, via intravenous (into the vein) infusion per protocol.
- DrugDaunorubicin
Antineoplastic agent, via intravenous (into the vein) infusion per protocol.
Locations (2)
- Yale Cancer CenterNew Haven, Connecticut
- Dana-Farber Cancer InstituteBoston, Massachusetts