A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

NCT07498465 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: PEPN2513NCI-2026-01768UM1CA228823
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial tests the safety, best dose, and effectiveness of revumenib given as maintenance therapy after standard hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia, acute myeloid leukemia, or mixed phenotype acute leukemia. Revumenib binds to a protein called menin, which prevents menin from interacting with another protein called MLL. This results in an inhibition of the proliferation of leukemic cells with certain genetic alterations. Revumenib may inhibit the survival, growth, transformation and proliferation of certain kinds of leukemia cells. It is approved for the treatment of patients with certain types of acute leukemia, but it is not approved for maintenance therapy (treatment that aims to prevent cancer from coming back) after HSCT.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Mixed Phenotype Acute Leukemia; Mixed Phenotype Acute Leukemia

Outcome Measures

Primary Outcomes (6)

• Maximum tolerated dose (MTD)

  Will use the Bayesian Optimal Interval (BOIN) design to estimate the MTD. The BOIN design with up to three pre-defined dose levels will estimate the MTD.

  During cycles 1 and 2 (cycle length = 28 days)

• Recommended phase 2 dose (RP2D)

  Will use the BOIN design to estimate the RP2D. The BOIN design with up to three pre-defined dose levels will estimate the RP2D.

  During cycles 1 and 2 (cycle length = 28 days)

• Area under the concentration time curve of revumenib

  Median and range of the area under the concentration time curve of revumenib determined by sampling on cycle 1 day 7 at time 0, 0.25, 0.5, 1, 2, 4, and 6 hours post dose by study part and dose level.

  Up to day 7

• Maximum concentration of the time curve of revumenib

  Median and range of the maximum concentration of revumenib determined by sampling on cycle 1 day 7 at time 0, 0.25, 0.5, 1, 2, 4, and 6 hours post dose by study part and dose level.

  Up to day 7

• Half-life of revumenib

  Median and range of the half-life of revumenib determined by sampling on cycle 1 day 7 at time 0, 0.25, 0.5, 1, 2, 4, and 6 hours post dose by study part and dose level.

  Up to day 7

• Clearance of revumenib

  Median and range of the clearance of revumenib determined by sampling on cycle 1 day 7 at time 0, 0.25, 0.5, 1, 2, 4, and 6 hours post dose by study part and dose level.

  Up to day 7

Secondary Outcomes (4)

• Relapse free survival

  At 2 years

• Incidence of treatment-related adverse events

  Up to 12 cycles (cycle length = 28 days)

• Proportion of patients who complete 12 cycles of maintenance therapy

  Up to 12 cycles (cycle length = 28 days)

• Proportion of patients who discontinue therapy due to treatment-related adverse events

  Up to 12 cycles (cycle length = 28 days)

Other Outcomes (5)

• Cumulative incidence of transplant-related mortality

  Up to 1 year follow-up

• Cumulative incidence of transplant-related relapse

  Up to 1 year follow-up

• Overall survival

  Up to 1 year follow-up

Study Arms (1)

Treatment (revumenib)

EXPERIMENTAL

Starting 42-100 days after HSCT, patients receive revumenib PO or via NG- or G-tube every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive optional intrathecal therapy (methotrexate IT or cytarabine IT or methotrexate, hydrocortisone, and cytarabine IT) at the discretion of the physician on study. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial. Patients may undergo ECHO and radiologic assessment as clinically indicated.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography Test; Drug: Methotrexate; Procedure: Radiologic Examination; Drug: Revumenib; Drug: Therapeutic Hydrocortisone

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

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

Treatment (revumenib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (revumenib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (revumenib)

Cytarabine DRUG

Given IT

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)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (revumenib)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (revumenib)

Radiologic Examination PROCEDURE

Undergo radiologic assessment

Also known as: Radiologic Evaluation, Radiologic Exam

Treatment (revumenib)

Revumenib DRUG

Given PO or via NG- or G-tube

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)

Therapeutic Hydrocortisone DRUG

Given IT

Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, Hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid

Treatment (revumenib)

Eligibility Criteria

• Age: 30 Days - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥ 30 days and \< 22 years of age
• PLEASE NOTE: Eligibility criteria to enroll onto Step 1 for the treatment trial is \< 22 years of age at the time of Step 1 enrollment. Please plan accordingly to ensure that patients who are screened with Step 0 will be at an eligible age at the time of enrollment onto Step 1. Patients who are 21 at the time of screening who turn 22 at the time of enrollment onto Step 1 will not be eligible to enroll onto the study
• Patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL) with a KMT2a rearrangement, NUP98 rearrangement, or NMP1 mutation confirmed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA) certified laboratory. Patients with a history of isolated or combined central nervous system (CNS) or extramedullary disease are eligible if they have no evidence of active CNS or extramedullary disease at the time of trial enrollment (Step 0) and treatment enrollment (Step 1). Eligible patients with histories of isolated or combined CNS or extramedullary disease at time of relapse are required to be in complete remission at time of transplant to be eligible for this study
• AML and MPAL must be in morphologic complete remission confirmed by multiparameter flow (MDF) testing (with or without detectable minimal residual disease \[MRD\]). ALL must have bone marrow MRD \< 0.1%
• Pre-HSCT bone marrow:
• Assessment of disease status (complete response \[CR\] and minimal residual disease \[MRD\]) by multiparameter flow cytometry will be performed on bone marrow aspirate samples locally. Disease assessment will be required within 30 days prior to the start date of HSCT to determine CR (as part of the Step 0 screening criteria). Patients with CNS or extramedullary disease within 14 days prior to the start of the HSCT condition regimen are not eligible
• Human immunodeficiency virus (HIV)-infected patients are eligible for this trial if the following criteria are met:
• No history of HIV complications with the exception of CD4 count \< 200 cells/mm\^3
• No antiretroviral therapy with overlapping toxicity such as myelosuppression
• CD4 count \> 500 cells/mm\^3 prior to the diagnosis of newly diagnosed, relapsed, refractory AML
• HIV viral loads below the limit of detection within 6 months, as long as the patient is NOT receiving anti-retroviral agents that may interact with revumenib
• No history of highly active antiretroviral therapy (HAART)-resistant HIV
• Lansky/Karnofsky performance status ≥ 70%
• Must be receiving an allogeneic hematopoietic stem cell transplant (all graft and donor types will be eligible)
• Must be receiving myeloablative conditioning as defined by Center for International Blood and Marrow Transplant Research (CIBMTR) criteria

You may not qualify if:

• Participants who have had a previous hematopoietic stem cell transplantation
• Participants who previously experienced a serious toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] grade 4) attributed to revumenib (probably or definitely related)
• Participants who previously experienced a relapse while receiving revumenib
• Patients diagnosed with Down syndrome
• Patients known to have one of the following syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman syndrome, or any other known bone marrow failure syndrome
• Patients with a secondary KMT2A-r leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy
• Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrythmia in the past 6 months prior to study enrollment
• AML with FLT3 ITD or other activating mutation, unless disease has proven unresponsive to TKI therapy or patient has experienced serious TKI related toxicity
• Estimated glomerular filtration rate (GFR) of \< 60 mL/min/1.73 m\^2
• Cardiac ejection fraction \< 50% or shortening fraction \< 27% (ECHO may be performed 3 months prior)
• Clinical evidence of pulmonary disease or need for continuous supplemental oxygen for greater than 24 hours
• Uncontrolled infection
• Patients who have received another investigational drug within 30 days prior to Step 0 enrollment
• Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study and for 4 months after the last revumenib dose. Abstinence is an acceptable method of birth control
• Patients who are currently receiving another investigational drug are not eligible.

Sponsors & Collaborators

• Children's Oncology Group: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute

Interventions

Specimen Handling; Biopsy; Cytarabine; Methotrexate; merphos; X-Rays; revumenib; Hydrocortisone

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

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; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Ben K Watkins

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 27, 2026
• Study Start: September 10, 2026
• Primary Completion (Estimated): November 12, 2028
• Study Completion (Estimated): November 12, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04