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

A Phase 1 Trial of the Menin Inhibitor SNDX-5613 (Revumenib) (NSC# 852942) for Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Mixed Phenotype Acute Leukemia; Childhood Mixed Phenotype Acute Leukemia
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Methotrexate; Drug: Therapeutic Hydrocortisone; Drug: Cytarabine; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Radiologic Examination; Drug: Revumenib

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of revumenib monotherapy administered as maintenance therapy, orally post-HSCT, on continuous 28-day cycles for patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL).

II. To characterize the steady state pharmacokinetics of revumenib administered as post-HSCT maintenance in children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL).

SECONDARY OBJECTIVES:

I. To preliminarily estimate the 2-year relapse free survival of patients receiving revumenib as post-HSCT maintenance therapy at the MTD/RP2D, within the confines of a phase 1 study.

II. To describe treatment related adverse events in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy up to 12 cycles.

III. To estimate the proportion of patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy who complete 12 cycles of maintenance therapy.

IV. To estimate the proportion of patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy who discontinue therapy due to treatment related adverse events.

EXPLORATORY OBJECTIVES:

I. To estimate the cumulative incidence of transplant-related mortality in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles.

II. To estimate the cumulative incidence of transplant-related relapse in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles.

III. To preliminarily estimate overall survival and disease-free survival in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles, within the confines of a phase 1 study.

IV. To estimate the cumulative incidence of acute and chronic graft versus host disease (GVHD) in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles.

OUTLINE: This is a dose-escalation study of revumenib followed by a dose-expansion study.

Starting 42-100 days after HSCT, patients receive revumenib orally (PO) or via nasogastric (NG)- or gastric (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 intrathecally [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 echocardiography (ECHO) and radiologic assessment as clinically indicated.

After completion of study treatment, patients are followed for up to 1 year.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• STEP 0 PRE-TRANSPLANT INCLUSION CRITERIA:

• 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
• STEP 1 INCLUSION CRITERIA:
• Patients must be ≥ 30 days and < 22 years of age at the time of study enrollment to Step 0 and Step 1

• Post-HSCT bone marrow:

  • Assessment of disease status (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 enrollment onto Step 1 to confirm MRD negativity (as part of the Step 1 Enrollment eligibility criteria). Disease must be in complete remission with marrow minimal residual disease < 0.05% for AML and < 0.01% for ALL by MDF. Patients with CNS or extramedullary disease post-HSCT are not eligible
• Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

• Patients must have recovered from the acute pre-transplant conditioning regimen related toxicities. If, after 42-100 days post-transplant, the eligibility criteria are met in criteria below the patient is considered to have recovered adequately

  • Pre-transplant exposure to revumenib will be allowed with the exception of patients who experienced a serious toxicity (CTCAE grade 4) attributed to revumenib (probably or definitely related) or those that experienced progression or relapse while receiving revumenib
• For patients ≤ 17 years old estimated GFR (eGFR) ≥ 60 mL/min/1.73 m^2 "Bedside" Schwartz formula OR for any age group a 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m2 OR a GFR ≥ 60 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
• For patients > 17 years old the Cockroft-Gault equation should be utilized to calculate eGFR OR for any age group a 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m2 OR a GFR ≥ 60 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 3 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment)
• Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment)
• Albumin ≥ 2 g/dL (must be performed within 7 days prior to enrollment)
• Shortening fraction of > 27% by echocardiogram, or ejection fraction of > 50% by gated radionuclide study with no evidence of congestive heart failure
• Ejection fraction of > 50% by gated radionuclide study with no evidence of congestive heart failure
• Corrected QT interval (QTc) < 450 ms
• No evidence of pulmonary disease and without need for continuous supplemental oxygen
• Potassium > 3.5mEq/L (supplementation allowed) (must be performed within 7 days prior to enrollment)
• Magnesium ≥ 1.6mg/dL (supplementation allowed) (must be performed within 7 days prior to enrollment)
• For patients with leukemia: platelet count ≥ 50,000 µL (without requirement for platelet transfusion within the last 7 days) (must be performed within 7 days prior to enrollment)
• For patients with leukemia: hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions) (must be performed within 7 days prior to enrollment)
• For patients with leukemia: absolute neutrophil count ≥ 1,000 µL with no myeloid growth factor support within the last 3 days (must be performed within 7 days prior to enrollment)

Exclusion Criteria:

• STEP 0 PRE-TRANSPLANT EXCLUSION CRITERIA:
• 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
• STEP 1 EXCLUSION CRITERIA:
• 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.
• Patients who are currently receiving other anti-cancer agents are not eligible. Patients receiving intrathecal chemotherapy in the prior 14 days are eligible
• Moderate or strong CYP3A4 inducers are prohibited during treatment. These agents should be discontinued at least 7 days prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitors is permitted with appropriate revumenib dose modification
• Avoid concomitant use with other drugs with a known potential to prolong QTc interval
• Patient is not able to start the first cycle of revumenib from day +42 through day +100 post-HSCT
• Patients with graft loss are not eligible
• Patients with steroid refractory or dependent acute grade 3-4 graft versus host disease (GVHD) are not eligible
• Patients who have an uncontrolled viral, bacterial, fungal, or protozoal infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (revumenib); 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; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Jylamvo; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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; Drug: Cytarabine; Given IT; Other Names: .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; Procedure: Bone Marrow Aspiration; Undergo bone marrow aspiration; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Procedure: Echocardiography Test; Undergo ECHO; Other Names: Echocardiography; EC; Procedure: Radiologic Examination; Undergo radiologic assessment; Other Names: Radiologic Evaluation; Radiologic Exam; Drug: Revumenib; Given PO or via NG- or G-tube; Other Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse free survival	Median relapse-free survival time will be estimated with 95% confidence intervals. 12-month relapse-free rates will also be estimated with 95 confidence intervals.	At 2 years
Incidence of treatment-related adverse events	Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.	Up to 12 cycles (cycle length = 28 days)
Proportion of patients who complete 12 cycles of maintenance therapy	The percent of adverse event-evaluable patients who successfully complete 12-cycles of maintenance therapy with revumenib will be estimated with a 95% confidence interval. Evaluable patients who do not complete 12-cycles of maintenance therapy for any reason will be considered a failure, and those who complete 12-cycles will be considered a success.	Up to 12 cycles (cycle length = 28 days)
Proportion of patients who discontinue therapy due to treatment-related adverse events	The percent of adverse event-evaluable patients without discontinuation-related adverse events will be estimated with a 95% confidence interval.	Up to 12 cycles (cycle length = 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of transplant-related mortality		Up to 1 year follow-up
Cumulative incidence of transplant-related relapse	Post-hematopoietic stem cell transplant (HSCT) relapse will be analyzed using competing risk analysis to estimate time-to-relapse within 12-months of enrollment. Competing risks will include deaths due to any cause. Patients who do not relapse will be censored for the event at the last date of follow-up or 12-months, whichever comes first. Cumulative incident functions will be estimated for all response-evaluable patients.	Up to 1 year follow-up
Overall survival	Disease response will be reported descriptively.	Up to 1 year follow-up
Disease-free survival	Disease response will be reported descriptively.	Up to 1 year follow-up
Cumulative incidence of acute and chronic graft versus host disease		Up to 1 year follow-up

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Investigators: Principal Investigator: Ben K Watkins, Pediatric Early Phase Clinical Trial Network

Study record dates

Study Major Dates

• Study Start (Estimated): September 10, 2026
• Primary Completion (Estimated): November 12, 2028
• Study Completion (Estimated): November 12, 2028

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Physical Phenomena; Polycyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnanes; Steroids; Fused-Ring Compounds; Diagnostic Techniques, Surgical; Nucleosides; Pterins; Pteridines; Arabinonucleosides; Aminopterin; Electromagnetic Phenomena; Magnetic Phenomena; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Methotrexate; Cytarabine; Hydrocortisone; Biopsy; Specimen Handling; X-Rays; merphos; revumenib
• Other Study ID Numbers: PEPN2513 (Other Identifier: CTEP); UM1CA228823 (U.S. NIH Grant/Contract); NCI-2026-01768 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes