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Revumenib in Combination With 7+3 + Midostaurin in AML

ConditionsAcute Myeloid LeukemiaAML, AdultAML With Gene MutationsAMLLeukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRichard Stone, MD

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

  • Revumenib

    Drug

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

  • Midostaurin

    Drug

    Kinase inhibitor, capsule taken orally per protocol.

  • Cytarabine

    Drug

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

  • Daunorubicin

    Drug

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

Treatment groups

22 Participants
are divided into 2 treatment groups
Group A: Dose Escalation RevumenibExperimental treatment 4 interventions
Group B: Dose-Expansion RevumenibExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Number of Participants Experiencing Dose Limiting Toxicity (DLT)

Detailed DLT consideration outline in protocol section 5.4.

Time frame
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.

Time frame
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.

Time frame
Up to 12 weeks

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
Up to 12 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Richard Stone, MD

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

Syndax Pharmaceuticals

Collaborator

Source ClinicalTrials.gov
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