Recruiting
Phase 1

SNDX-5613 & Daunorubicin, Cytarabine

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05886049

Conditions

Acute Myeloid Leukemia

Acute Myeloid Leukemia With KMT2A Rearrangement

Acute Myeloid Leukemia With NPM1 Mutation

Secondary Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Cytarabine

Daunorubicin

Study Details

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

Acute Myeloid Leukemia With KMT2A Rearrangement

Acute Myeloid Leukemia With NPM1 Mutation

Secondary Acute Myeloid Leukemia

Study ID

NCT05886049

Start date

Jun 20, 2024

Status verified date

Aug, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Dose escalation: Patients ages 18-75 years at time of diagnosis with NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype with high-risk features (adverse risk genetics per European LeukemiaNet \[ELN\] 2022 criteria, age ≥ 60 years, or secondary AML defined as either arising from a prior hematological malignancy or therapy-related), MLL (KMT2A) rearranged or NUP98 altered, untreated AML and who are candidates for intensive induction chemotherapy. Patients with CD33+ AML are eligible for this protocol.
  • Dose expansion: Patients ages 18-75 years at time of diagnosis with NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype (any patient-does not require high-risk features), MLL (KMT2A) rearranged, or NUP98 altered, untreated AML and who are candidates for intensive induction chemotherapy. Patients with CD33+ AML are eligible for this protocol
  • 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%). Patients over the age of 65 must have an ECOG performance status of 0-1
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except for patients with Gilbert's syndrome where required to be ≤ 3 x institutional ULN
  • 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 180 days until the last dose of study treatment. They must also refrain from sperm donation from screening visit until 180 days following the last dose of study treatment
  • Patients must have previously untreated AML with no prior treatment other than hydroxyurea or intrathecal chemotherapy for central nervous system (CNS) prophylaxis/treatment. 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
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SNDX-5613, daunorubicin or cytarabine
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • Patient must not have received known strong or moderate CYP3A4 inhibitors, or strong CYP3A4 inducers (with the exception of antifungal prophylaxis with azoles) 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)
  • Untreated, active central nervous system (CNS) involvement by AML. Patients are allowed to undergoing diagnostic lumbar puncture (LP) with intrathecal chemotherapy while on study
  • 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

Study Design

Enrollment

38 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (revumenib, daunorubicin, cytarabine)

See Detailed Description.

Interventions

Biospecimen Collection

Undergo collection of blood

Bone Marrow Aspiration

Undergo bone marrow aspiration and biopsy

Bone Marrow Biopsy

Undergo bone marrow aspiration and biopsy

Cytarabine

Given IV

Daunorubicin

Given IV

Multigated Acquisition Scan

Undergo MUGA

Revumenib

Given PO

Transthoracic Echocardiography Test

Undergo transthoracic ECHO

Primary outcome measure

  • Recommended dose for expansion (RDE) for Induction [ Time Frame: From day 1 to 42 of Induction or Re-Induction ]
  • RDE for Consolidation [ 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 [ 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 ]

Central Contacts and Locations

Locations

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Kiran Naqvi

UM Sylvester Comprehensive Cancer Center at Aventura

Recruiting

Aventura, Florida, United States, 33180

Contacts

Site Public Contact

954-461-2180

Principal Investigator:

Sangeetha Venugopal

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Sangeetha Venugopal

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Sangeetha Venugopal

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Sangeetha Venugopal

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Sangeetha Venugopal

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Olatoyosi M. Odenike

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Jesus Gonzalez Lugo

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Jesus Gonzalez Lugo

University of Kansas Hospital-Indian Creek Campus

Recruiting

Overland Park, Kansas, United States, 66211

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Jesus Gonzalez Lugo

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Jesus Gonzalez Lugo

University of Maryland/Greenebaum Cancer Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Site Public Contact

800-888-8823

Principal Investigator:

Vu H. Duong

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

877-442-3324

Principal Investigator:

Richard M. Stone

UNC Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Site Public Contact

877-668-0683cancerclinicaltrials@med.unc.edu

Principal Investigator:

Joshua F. Zeidner

Carolinas Medical Center/Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28203

Contacts

Site Public Contact

800-804-9376

Principal Investigator:

Brittany K. Ragon

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Matthew J. Wieduwilt

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Emily K. Curran

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Alice S. Mims

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Emily K. Curran

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Mohamad Khawandanah

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100cancerinfo@hci.utah.edu

Principal Investigator:

Paul J. Shami

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 25, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-25.