A Phase 1 interventional study of Biospecimen Collection and Bone Marrow Aspiration in Acute Myeloid Leukemia, Acute Myeloid Leukemia With KMT2A Rearrangement and Acute Myeloid Leukemia With NPM1 Mutation, sponsored by National Cancer Institute (NCI). Recruiting at 23 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase Ib trial tests the safety, side effects, and best dose of SNDX-5613 when given in combination with the standard chemotherapy treatment (daunorubicin and cytarabine) in treating patients with newly diagnosed acute myeloid leukemia that has changes in the NPM1 gene or MLL/KMT2A gene. SNDX-5613 blocks signals passed from one molecule to another inside cancer cells that are needed for cancer cell survival. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding SNDX-5613 to the standard chemotherapy treatment may be able to shrink or stabilize the cancer for longer than the standard chemotherapy treatment alone.
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) and safety of revumenib (SNDX-5613) combined with 7 + 3 induction in newly diagnosed, untreated patients with NPM1-mutated/FLT3-ITD wild type and NPM1-mutated/FLT3-TKD wild type, MLL(KMT2A)-rearranged, or NUP98 altered acute myeloid leukemia (AML) who are ≥ 18-75 years old who are candidates for intensive induction therapy.
II. To determine the RP2D and safety of SNDX-5613 combined with one cycle of consolidation with high dose cytarabine in newly diagnosed patients with AML in complete response/complete response with incomplete platelet recovery (CR/CRp) (platelet recovery ≥ 75,000) after intensive induction therapy with 7+3 for NPM1-mutated/FLT3-ITD wild type and NPM1-mutated/FLT3-TKD wild type, MLL (KMT2A)-rearranged or NUP98 alterations who are ≥ 18-75 years old and are candidates for intensive therapy.
III. To evaluate the effect of single-agent SNDX-5613 on AML cell cycle state across major differentiation states (stem/progenitor, mature blasts, etc.).
SECONDARY OBJECTIVES:
I. Evaluate the pharmacokinetics of SNDX-5613 and SNDX-5613 metabolites with this combination regimen and with or without antifungal agents.
II. To determine the number of patients with CR/complete response with incomplete bone marrow recovery (CRi) out of the total number of patients treated at each dose level of this regimen.
EXPLORATORY OBJECTIVES:
I. Explore potential biomarker indicators of response and resistance in AML samples.
II. To determine the measurable residual disease negative (MRD) response (CR/Cri) and its relation to CR/Cri status out of the total number of patients treated at each dose level of this regimen.
III. Determine number of patients that undergo hematopoietic stem cell transplant (HSCT) out of the total number of patients treated at each dose level of this regimen.
IV. Assess changes in OATP1B and CYP3A plasma biomarkers during treatment with SNDX-5613 with or without antifungal agents.
V. Determine duration of response.
OUTLINE: This is a phase Ib, dose-escalation study of revumenib followed by a dose-expansion study.
INDUCTION: Patients receive revumenib orally (PO) every 12 hours (Q12h) on days 2-28, daunorubicin intravenously (IV) over 15 to 30 minutes on days 1-3, and cytarabine by continuous IV infusion (CIV) on days 1-7 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response to Induction treatment continue to Consolidation treatment. Patients with persistent disease continue to Re-Induction treatment. Patients also undergo a transthoracic echocardiogram (ECHO) or multigated acquisition scan (MUGA) during screening, bone marrow aspiration and biopsy during screening and at the end of Induction, and collection of blood during screening, on days 2, 3, 15, and at the end of Induction.
RE-INDUCTION: Patients receive revumenib PO Q12h on days 2-28, daunorubicin IV over 15 to 30 minutes on days 1-2, and cytarabine CIV on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients also undergo a transthoracic ECHO or MUGA on day 1 and bone marrow aspiration and biopsy at the end of Re-Induction.
Patients who achieve CR or CRp to Induction or Re-Induction treatment continue to Consolidation.
CONSOLIDATION: Patients receive revumenib PO Q12h on days 2-28 and cytarabine over 3 hours every 12 hours on days 1-3 of each cycle. Cycles repeat every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at the end of Consolidation, and collection of blood on days 2, 3, 15, and at the end of Consolidation.
After completion of study treatment, patients are followed for up to 2 years or until death or relapse, whichever occurs first.
2,971 studies on the registry are indexed under Leukemia, Myeloid, Acute; 745 are open to participants now.
This study's planned enrollment of 38 is close to the median of 41 across 2,509 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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Exclusion Criteria:
See Detailed Description.
Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Cytarabine · Drug: Daunorubicin · Procedure: Multigated Acquisition Scan · Drug: Revumenib · Procedure: Transthoracic Echocardiography Test
Undergo collection of blood
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Given IV
Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Given IV
Also known as: Daunomycin, Daunorrubicina, DNR, Leukaemomycin C, Rubidomycin, Rubomycin C
Undergo MUGA
Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning
Given PO
Also known as: Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613, Menin-MLL Inhibitor SNDX-5613, Menin-MLL Interaction Inhibitor SNDX-5613, SNDX 5613, SNDX-5613, SNDX5613
Undergo transthoracic ECHO
Also known as: TRANSTHORACIC ECHOCARDIOGRAPHY, TTE
Recommended dose for expansion (RDE) for Induction
Will be determined based on the totality of safety, tolerability, clinical activity, and pharmacokinetic (PK) data as appropriate. The tolerability of doses administered in cycles after the dose limiting toxicity (DLT) observation window should be taken into account in determination of the RDE. For all patients who receive at least one dose of any of the study drug(s), adverse events will be documented and summarized by type, grade, severity, and attribution using the Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 criteria. In addition, the number of treatment cycles received and reasons for going off treatment will be summarized to assess treatment tolerability.
Time frame: From day 1 to 42 of Induction or Re-Induction
RDE for Consolidation
Will be determined based on the totality of safety, tolerability, clinical activity, and PK data as appropriate. The tolerability of doses administered in cycles after the DLT observation window should be taken into account in determination of the RDE.For all patients who receive at least one dose of any of the study drug(s), adverse events will be documented and summarized by type, grade, severity, and attribution using the CTCAE v5.0 criteria. In addition, the number of treatment cycles received and reasons for going off treatment will be summarized to assess treatment tolerability.
Time frame: From day 1 to 42 of Consolidation or until full count recovery with recovery to grade 1 toxicity from treatment, whichever comes first
Recommended phase 2 dose for expansion cohort
RP2D of induction will be determined based on isotonic regression. Specifically, the RP2D that is selected is the dose for which the isotonic estimate of the toxicity rate is closest to the targeted DLT (i.e., 20%) via "BOIN" software \[MD Anderson\]) and will also factor in data such as PK/pharmacodynamic data to determine the biologically effective dose. For all patients who receive at least one dose of any of the study drug(s), adverse events will be documented and summarized by type, grade, severity, and attribution using the CTCAE v5.0 criteria. In addition, the number of treatment cycles received and reasons for going off treatment will be summarized to assess treatment tolerability.
Time frame: From day 1 of Induction to day 42 of Consolidation or until full count recovery with recovery to grade 1 toxicity from treatment, whichever comes first
Complete response/complete response with incomplete count recovery (CR/Cri) rate
Will be calculated by the number of patients achieving CR/CRi response out of the total number of patients treated on both the dose-escalation and expansion portions with 95% exact binomial confidence interval.
Time frame: At the end of cycle 1 of consolidation
Pharmacokinetics (PK) of revumenib (SNDX-5613)
The PK sampling is designed to enable estimation of individual PK parameters of SNDX-5613 and it's metabolite using standard noncompartmental methods. The primary analysis will compare SNDX-5613 exposure (area under the curve from zero to infinity) on day 2 (before strong antifungal agent administration starting on Day 4 after completion of anthracycline) and steady-state exposure (area under plasma concentration-time curve over dosing interval) on day 15 (after administration of antifungal agent).
Time frame: Cycle 1, day 2 at pre-treatment, 0.5, 1.0, 2.0, 4.0, 8.0 hours (hr); Cycle 1 day 3 at 12 hr; cycle 1 day 15 at pre-treatment, 0.5, 1.0, 2.0, 4.0, and 8.0 hr
Minimal residual disease (MRD) negative status
MRD negative status is defined as the following for each genomic subgroup: 1) NPM1mutated/FLT3 ITD and FLT3 TKD wildtype: negative NPM1 by polymerase chain reaction testing on bone marrow after cycle 1 of consolidation (or after induction if unable to receive consolidation) or 2) MLL (KMT2A) rearrangement: negative multi-parameter flow cytometry (flow cutoff 10\^-3) after induction chemotherapy. The number of patients with MRD negative status and the relationship to clinical response will be described at each time point of interest. Swimmer plots will be utilized to visually display how MRD status improves/changes over time.
Time frame: From day 1 to 42 of Induction, Re-Induction, and Consolidation
Duration of response
Swimmer plots will be utilized to visually display how response improves/changes over time.
Time frame: From the first date of CRi or CR until relapse or death from any cause, whichever occurs first, assessed up to 2 years after completion of study treatment
Overall survival
Median survival will be estimated with 95% confidence interval using Kaplan-Meier method. Swimmer plots will be utilized to capture milestone events including relapse of disease and death for each patient within a given dose level.
Time frame: From the date on treatment until the date of death from any cause, assessed up to 2 years after completion of study treatment
Number of patients who undergo hematopoietic stem cell transplant (HSCT) out of the total number patients treated at each dose level
Will be described. Swimmer plots will be utilized to capture receipt of HSCT for each patient within a given dose level.
Time frame: Up to 30 days after completion of study treatment
Changes in OATP1B and CYP3A biomarkers
Will also explore SNDX-5613 exposure and it's relevant metabolites as a function of 3 antifungal groups (moderate CYP3A4 inhibitors, strong CYP3A4 inhibitors, no azole antifungal/other). Will include descriptive comparisons of SNDX-5613 PK and exposure parameters through summary statistical and graphical presentations to identify patterns with historical data from 1) single-agent SNDX-5613; 2) OATP1B1/3 plasma biomarker exposure toxicity and efficacy; and 3) toxicity and efficacy outcomes.
Time frame: Baseline to cycle 1, day 2 at pre-treatment, 0.5, 1.0, 2.0, 4.0, 8.0 hours (hr); Cycle 1 day 3 at 12 hr; cycle 1 day 15 at pre-treatment, 0.5, 1.0, 2.0, 4.0, and 8.0 hr
Plan to share: Yes — "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."
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