Trial of Revumenib Plus FLA Chemotherapy for Children With Relapsed or Refractory NUP98-rearranged AML."

NCT07686107 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: T2023-004
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if Revumenib in combination with Fludarabine and Cytarabine can treat children with NUP98-rearranged relapsed or refractory Acute Myeloid Leukemia. The main question it aims to answer is: What is the Best Overall Response Rate by morphologic response criteria after up to two cycles of revumenib in combination with fludarabine and cytarabine (FLA) chemotherapy? Participants will receive up to two cycles of Revumenib in combination with fludarabine and cytarabine with intrathecal triple therapy. Participant may also receive a stem cell transplant followed by Revumenib monotherapy if it is necessary. Up to 27 children and young adults will be enrolled.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BOR) by morphologic response criteria

  The best Overall Response rate according to morphologic response (Morph-CR/CRi/CRp) after up to 2 cycles

  At the end of Cycle 1 and Cycle 2 (each cycle is 28 days)

Study Arms (1)

Part 1

EXPERIMENTAL

Revumenib -Days 1-28 Fludarabine -Days 1-5 Cytarabine -Days 1-5 IT Therapy Triples (Methotrexate, Hydrocortisone, Cytarabine) -Day 0. May receive with marrow done at the end of the previous course. For CNS2 and CNS3 patients, in Cycle 1 continue weekly for 3 to 6 total doses or until 3 negative CSF samples, whichever comes first.

Drug: Revumenib; Drug: Fludarabine; Drug: Cytarabine (Ara-C); Drug: Methotrexate (IT); Drug: Hydrocortisone (intrathecal); Drug: Cytarabine (intrathecal)

Interventions

Revumenib DRUG

Patients under 40 kg, and those unable to swallow pills, must receive oral suspension (40 mg/mL): * \< 40 kg: 95 mg/m2 (max 160 mg/dose) orally twice daily * ≥ 40 kg (flat-dose): 160 mg orally twice daily * Round to the nearest markings on the syringe, within 10% of the calculated dose Patients ≥ 40 kg that are able to swallow pills: \- 160 mg orally twice daily

Part 1

Fludarabine DRUG

* 5 mg for patients with BSA 0.25-0.29 * 6.25 mg for patients with BSA 0.3-0.34 * 8.75 mg for patients with BSA 0.35-0.39 * 10 mg for patients with BSA 0.4-0.44 * 12.5 mg for patients with BSA 0.45-0.49 * 15 mg for patients with BSA 0.5-0.54 * 16.25 mg for patients with BSA 0.55-0.59 * 30 mg/m2/dose for patients with BSA \> 0.6

Part 1

Cytarabine (Ara-C) DRUG

* 300 mg for patients with BSA 0.25-0.29 * 420 mg for patients with BSA 0.3-0.34 * 560 mg for patients with BSA 0.35-0.39 * 680 mg for patients with BSA 0.4-0.44 * 820 mg for patients with BSA 0.45-0.49 * 960 mg for patients with BSA 0.5-0.54 * 1100 mg for patients with BSA 0.55-0.59 * 2000 mg/m2/dose for patients with BSA \> 0.6

Part 1

Methotrexate (IT) DRUG

Given intrathecally * 6 mg for patients \> 30 days - \< 1 year * 8 mg for patients \> 1 - \< 2 years * 10 mg for patients \> 2 - \< 3 years * 12 mg for patients \> 3 years

Part 1

Hydrocortisone (intrathecal) DRUG

Given intrathecally * 12 mg for patients \> 30 days - \< 1 year * 16 mg for patients \> 1 - \< 2 years * 20 mg for patients \> 2 - \< 3 years * 24 mg for patients \> 3 years

Part 1

Cytarabine (intrathecal) DRUG

Given intrathecally * 18 mg for patients \> 30 days - \< 1 year * 24 mg for patients \> 1 - \< 2 years * 30 mg for patients \> 2 - \< 3 years * 36 mg for patients \> 3 years

Part 1

Eligibility Criteria

• Age: 1 Year - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Patients must be \> 1 year and \< 22 years of age at time of enrollment.
• Diagnosis Patients must have NUP98-r AML (according to WHO Classification of Hematolymphoid Tumors (5th Edition)) that is either refractory to or is in first relapse following initial therapy. Documentation of prior known NUP98-r AML is sufficient.
• Definition of relapsed disease:
• Recurrent disease with ≥ 5% leukemic blasts by morphology in the bone marrow after having achieved morphologic remission (morph-CR). Patients who have received any other re-induction therapy following relapse will not be eligible.
• Morph-CR is defined as attainment of an M1 bone marrow (\< 5% morphologic leukemic blasts) no evidence of circulating leukemic blasts or extramedullary disease and with recovery of peripheral blood counts (ANC ≥ 500/µL and platelet count ≥ 50,000/µL).
• Definition of primary refractory disease:
• Refractory disease with ≥ 5% leukemic blasts by morphology in the bone marrow after one attempt at remission induction, which may consist of up to two different therapy courses (e.g., COG AAML1831 de novo therapy including Induction I and Induction II). Patients must not have received more than one remission induction remission attempt.
• White Blood Cell Count:
• White blood cell count must be \<25,000 cells/uL at the time of enrollment on the study. Cytoreduction with leukapheresis, hydroxyurea, and/or cytarabine (up to a total dose of 500 mg/m\^2) prior to enrollment is allowed.
• Performance Level Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (\> 50 Lansky or Karnofsky score). Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age (Appendix I). 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.
• CNS Disease Patients may have status of CNS1, CNS2, or asymptomatic CNS3 disease. Patients with symptomatic CNS 3 disease are ineligible.
• HIV-Infection HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial, provided antiretroviral therapy does not have clinically significant drug-drug interactions with revumenib.
• Prior Therapy:
• Patients must have recovered from all prior treatment-related toxicities to grade ≤1 or the patient's baseline and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
• Cytotoxic Chemotherapy: Must not have received within 14 days of entry onto this study, except for hydroxyurea or cytarabine

You may not qualify if:

• Isolated Extramedullary Disease: Patients with isolated extramedullary disease are ineligible.
• Prior diagnosis of acute lymphoblastic leukemia: Patients experiencing lineage switch to AML will not be eligible for this study.
• CNS3 Disease with clinical signs or neurologic symptoms suggestive of CNS leukemia at time of relapse, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome.
• Infection: Patients with documented active, uncontrolled infection at the time of study enrollment.
• Patients are excluded if they have:
• Positive blood culture within 48 hours of study enrollment;
• Fever above 38.2⁰C within 48 hours of study enrollment with clinical signs of infection. NOTE: Fever that is determined to be due to tumor burden does NOT exclude patients if there are documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
• A positive fungal culture within 30 days of study enrollment.
• Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections does not exclude patients.
• Cardiac: Patients with a history of congenital prolonged QT syndrome, congestive heart failure, or uncontrolled arrhythmia in the past 6 months prior to study enrollment.
• Gastrointestinal issues: Patients with gastrointestinal issues of the upper gastrointestinal tract that might affect oral drug absorption.
• Prior menin inhibitor therapy
• Patients with active GVHD are ineligible to enroll. Patients who are receiving systemic cyclosporine, tacrolimus, or other agents to prevent or treat either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible to enroll on the trial. Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible.
• Concomitant Medications CYP3A4 Inhibitors/Inducers: Systemically administered moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors should be discontinued for at least 5 half-lives or 7 days prior to enrollment (whichever is later) with the following exceptions: itraconazole, ketoconazole, posaconazole, or voriconazole.
• Corticosteroids: Patients who are receiving systemic corticosteroids are not eligible except when given as physiologic dosing (prednisone equivalent of ≤ 10 mg/day if ≥18 years and ≤ 10 mg/m2/day for patients \< 18 years is allowed).

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

revumenib; fludarabine; Cytarabine; Methotrexate; Hydrocortisone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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; 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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 7, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 22, 2026

Record last verified: 2026-07