Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene

NCT05886049 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2023-0414110596UM1CA186712
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

Acute Myeloid Leukemia With KMT2A Rearrangement; Acute Myeloid Leukemia With NPM1 Mutation

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) for Induction

  MTD of induction will be determined based on isotonic regression. Specifically, the MTD is selected as the dose for which the isotonic estimate of the toxicity rate is closest to the targeted dose-limiting toxicity (DLT) (i.e., 25%) via Bayesian Optimal Interval ("BOIN") software (MD Anderson). 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.

  From day 1 to 42 of Induction or Re-Induction

• Maximum tolerated dose (MTD) for Consolidation

  MTD of induction will be determined based on isotonic regression. Specifically, the MTD is selected as the dose for which the isotonic estimate of the toxicity rate is closest to the targeted DLT (i.e., 25%) via "BOIN" software (MD Anderson). 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.

  From day 1 to 42 of Consolidation

• Recommended phase 2 dose for expansion cohort

  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.

  From day 1 of Induction to day 42 of Consolidation

Secondary Outcomes (2)

• Pharmacokinetics (PK) of revumenib (SNDX-5613)

  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

• Complete response/complete response with incomplete count recovery (CR/Cri) rate

  At the end of cycle 1 of consolidation

Other Outcomes (7)

• Best response to Induction

  From day 1 to 42 of Induction or Re-Induction

• Best response overall

  Up to 30 days after completion of study treatment

• Minimal residual disease (MRD) negative status

  From day 1 to 42 of Induction, Re-Induction, and Consolidation

Study Arms (1)

Treatment (revumenib, daunorubicin, cytarabine)

EXPERIMENTAL

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

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (revumenib, daunorubicin, cytarabine)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (revumenib, daunorubicin, cytarabine)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (revumenib, daunorubicin, cytarabine)

Cytarabine DRUG

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

Treatment (revumenib, daunorubicin, cytarabine)

Daunorubicin DRUG

Given IV

Also known as: Daunomycin, Daunorrubicina, DNR, Leukaemomycin C, Rubidomycin, Rubomycin C

Treatment (revumenib, daunorubicin, cytarabine)

Multigated Acquisition Scan PROCEDURE

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

Treatment (revumenib, daunorubicin, cytarabine)

Revumenib DRUG

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

Treatment (revumenib, daunorubicin, cytarabine)

Transthoracic Echocardiography Test PROCEDURE

Undergo transthoracic ECHO

Also known as: TRANSTHORACIC ECHOCARDIOGRAPHY, TTE

Treatment (revumenib, daunorubicin, cytarabine)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Induction therapy: Patients ages 18-75 years at time of diagnosis with NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype or MLL (KMT2A) rearranged untreated AML and who are candidates for intensive induction chemotherapy
• Because no dosing or adverse event data are currently available on the use of SNDX-5613 in combination with daunorubicin and cytarabine in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Total bilirubin =\< 2 x institutional upper limit of normal (ULN), except for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal (ULN)
• Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 (via the Chronic Kidney Disease Epidemiology \[CKD-EPI\] glomerular filtration rate estimation)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Ejection fraction \>= 50% (or \>= 45% if no evidence of congestive heart failure \[CHF\] or other cardiac symptoms) by transthoracic echocardiogram (TTE) or multi-gated acquisition (MUGA) scan
• White blood cells (WBC) must be \< 25 x 10\^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped within 24 hours of initiation of protocol therapy. Must not have had any signs of leukostasis requiring cytoreduction
• Female patients of childbearing potential must agree to use 2 forms of contraception from screening visit until 120 days following the last dose of study treatment. Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from screening visit until 120 days until the last dose of study treatment. They must also refrain from sperm donation from screening visit until 120 days following the last dose of study treatment
• Patients must have previously untreated AML with no prior treatment other than hydroxyurea. No chemotherapy for AML outside of hydroxyurea for treatment of leukostasis or all-trans retinoic acid (ATRA) for initially suspected acute promyelocytic leukemia (APL) (that is ruled out) is allowed

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SNDX-5613, daunorubicin or cytarabine
• Patients with uncontrolled intercurrent illness that would make participation in this study unduly burdensome or unsafe for patient
• Patient must not have received known strong or moderate CYP3A4 inhibitors, or strong CYP3A4 inducers (with the exception of the antifungal) or sensitive/narrow therapeutic substrates of MATE1 within 7 days of enrollment. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Pregnant women are excluded from this study because SNDX-5613 is a menin-KMT2A inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SNDX-5613, breastfeeding should be discontinued if the mother is treated with SNDX-5613. These potential risks may also apply to other agents used in this study
• Isolated myeloid sarcoma (i.e., patients must have blood or marrow involvement with AML to enter the study)
• Acute promyelocytic leukemia (French-American-British \[FAB\] M3)
• Active central nervous system (CNS) involvement by AML
• Uncontrolled symptomatic disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
• Patients with Fridericia's correction formula (QTcF) \>= 450 ms at screening; patients with right, left, or partial bundle branch blocks or a pacemaker who are asymptomatic are eligible regardless of QTC if cleared by cardiology for enrollment in the trial. Any factors that increase the risk of QTc prolongation or risk of arrhythmic event such as congenital long QT syndrome or family history of long QT syndrome
• Patients who will exceed a lifetime anthracycline exposure of \> 550 mg/m\^2 daunorubicin or equivalent (or \> 400 mg/m\^2 daunorubicin or equivalent in the event of prior mediastinal radiation) if they receive the maximum potential exposure to anthracyclines per protocol (including both induction and reinduction cycles)
• Patients with any gastrointestinal issue of the upper gastrointestinal (GI) tract that might affect oral drug absorption or ingestion (eg, gastric bypass, gastroparesis, etc)
• Patients who have cirrhosis with a Child-Pugh score of B or C
• Patients with Down Syndrome due to higher rates of chemotherapy-associated toxicities, and may have different pharmacokinetics, as well. Toxicities that occur at higher frequencies include cardiotoxicity, a known risk of SNDX-5613 treatment (i.e., QTcF prolongation)
• Patients with myelodysplastic syndromes (MDS) treated with previous intensive induction regimens similar to 7+3

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (22)

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

SUSPENDED

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Biopsy; Cytarabine; Daunorubicin; revumenib

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Alice S Mims

  Ohio State University Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: June 2, 2023
• Study Start: June 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (22)