New combo therapy aims to improve AML treatment for patients with specific gene changes

NCT ID NCT05886049

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Aug 26, 2026 · Updated 8 times

Summary

This early-phase trial tests whether adding a menin inhibitor (SNDX-5613) to standard chemotherapy can better control acute myeloid leukemia (AML) in people with certain gene changes (NPM1 or MLL). About 38 newly diagnosed adults will receive the combination to find the safest dose and check for side effects. The goal is to see if the targeted drug helps shrink or stabilize the cancer longer than chemo alone.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

About 38 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jun 2024

Expected to finish

Dec 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 75 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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

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Conditions

The condition(s) this trial relates to.

acute myeloid leukemia acute myeloid leukemia with mutated NPM1 acute myeloid leukemia, MLL gene rearrangement therapy related acute myeloid leukemia and myelodysplastic syndrome

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Acute myeloid leukemia Acute myeloid leukemia with KMT2A rearrangement Acute myeloid leukemia with NPM1 mutation Secondary acute myeloid leukemia

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

22 sites. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Locations

Carolinas Medical Center/Levine Cancer Institute
RECRUITING

Charlotte, North Carolina, 28203, United States
Dana-Farber Cancer Institute
RECRUITING

Boston, Massachusetts, 02215, United States
Huntsman Cancer Institute/University of Utah
RECRUITING

Salt Lake City, Utah, 84112, United States

Contact Email: •••••@•••••
Ohio State University Comprehensive Cancer Center
RECRUITING

Columbus, Ohio, 43210, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING

Orange, California, 92868, United States

Contact Email: •••••@•••••
UM Sylvester Comprehensive Cancer Center at Aventura
RECRUITING

Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITING

Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITING

Deerfield Beach, Florida, 33442, United States
UM Sylvester Comprehensive Cancer Center at Plantation
RECRUITING

Plantation, Florida, 33324, United States
UNC Lineberger Comprehensive Cancer Center
RECRUITING

Chapel Hill, North Carolina, 27599, United States

Contact Email: •••••@•••••
University of California Davis Comprehensive Cancer Center
SUSPENDED

Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center
RECRUITING

Chicago, Illinois, 60637, United States

Contact Email: •••••@•••••
University of Cincinnati Cancer Center-UC Medical Center
RECRUITING

Cincinnati, Ohio, 45219, United States

Contact Email: •••••@•••••
University of Cincinnati Cancer Center-West Chester
RECRUITING

West Chester, Ohio, 45069, United States

Contact Email: •••••@•••••
University of Kansas Cancer Center
RECRUITING

Kansas City, Kansas, 66160, United States
University of Kansas Clinical Research Center
RECRUITING

Fairway, Kansas, 66205, United States
University of Kansas Hospital-Indian Creek Campus
RECRUITING

Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
RECRUITING

Westwood, Kansas, 66205, United States
University of Maryland/Greenebaum Cancer Center
RECRUITING

Baltimore, Maryland, 21201, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING

Miami, Florida, 33136, United States
University of Oklahoma Health Sciences Center
RECRUITING

Oklahoma City, Oklahoma, 73104, United States
University of Virginia Cancer Center
ACTIVE_NOT_RECRUITING

Charlottesville, Virginia, 22908, United States
Wake Forest University Health Sciences
RECRUITING

Winston-Salem, North Carolina, 27157, United States

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