Revumenib in Combination with Fludarabine and Cytarabine for Pediatric Refractory or Relapsed KMT2A-r, NUP98-r, or NPM1-mut Acute Myeloid Leukemia
- Trial ID
- 2025-521390-14-00
- Protocol
- STRIVE
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to estimate the overall response rate (ORR) in pediatric patients with refractory or relapsed acute myeloid leukemia (AML) harboring KMT2A-r, NUP98-r, or NPM1-mut genetic alterations, following up to two cycles of revumenib in combination with FLA chemotherapy. Clinical response is assessed using pediatric-specific criteria, including morphologic complete remission (morph-CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with platelet recovery (CRp). 5, 3
Secondary objectives include:
- Evaluation of safety and toxicity of the investigational treatment. 4
- Estimation of overall survival. 5
- Characterization of population pharmacokinetic (PopPK) parameters for revumenib and its primary metabolite, M1. 6
- Description of hematopoietic stem cell transplant (HSCT) rates following treatment.
- Collection of biomaterials for subsequent biological sub-studies.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of pediatric patients with acute myeloid leukemia, specifically those with refractory or relapsed KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated disease. Eligible participants include individuals aged more than 30 days to 18 years, including both males and females. Required clinical characteristics include a Lansky or Karnofsky score of ≥50% and adequate renal, hepatic, and cardiac function. Patients must have fully recovered from the acute toxic effects of prior anti-cancer therapies and must have a white blood cell count of less than 25,000/µL prior to enrollment. Additionally, specific intervals must have elapsed following prior chemotherapy, allogeneic stem cell transplantation, or cellular therapies.
Plans and Procedures
This Phase II clinical trial is designed to evaluate the efficacy of revumenib in combination with FLA chemotherapy, consisting of cytarabine and fludarabine, for the treatment of pediatric patients with refractory or relapsed acute myeloid leukemia characterized by KMT2A-r, NUP98-r, or NPM1-mut genetic alterations. The primary objective is to estimate the overall response rate using pediatric-specific response criteria after up to two treatment cycles. The study involves a screening process to confirm eligibility based on age, performance status, organ function, and specific molecular profiles. Following enrollment, participants receive the combination therapy via intravenous and oral administration. The trial is expected to conclude by February 2019, with recruitment beginning in February 2026. Specific conditions for early termination or withdrawal are governed by the adherence to the protocol and clinical safety requirements.
Treatment
The experimental treatment consists of revumenib, an orphan drug administered via the oral route. The medication is provided in tablet or oral solution pharmaceutical forms at a dosage of 540 mg.
The combination chemotherapy regimen includes cytarabine, which is administered as an intravenous injection at a dose of 2000 mg/m2. Additionally, fludarabine is administered through intravenous administration at a dose of 30 mg/m2.
Efficacy
The primary efficacy endpoint for this study is the estimation of the overall response rate (ORR). This assessment is conducted in patients with refractory or relapsed acute myeloid leukemia (AML) harboring KMT2A-r, NUP98-r, or NPM1-mut mutations. Efficacy is evaluated based on pediatric-specific response criteria, including morphologic complete remission (Ped-morph-CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with platelet recovery (CRp).
The ORR is estimated following the administration of up to two cycles of revumenib in combination with FLA chemotherapy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients must be > 30 days and ≤ 18 years of age at time of enrollment.
- Patients must have R/R KMT2A-translocation (KMT2A-r), NUP98-rearrangement (NUP98-r) or NPM1-mutation (NPM1-mut AML). History of known KMT2A-r, NUP98-r or NPM1-mut is sufficient. Definition of refractory/relapsed disease (patient must have one of the following): primary refractory disease (≥ 5% leukemic blasts) after 2 cycles of induction, or first recurrent disease (≥ 5% leukemic blasts) after having achieved remission (ped-morph-CR).
- ≥21 days must have elapsed since the patient’s last prior anti-cancer therapy (e.g., chemotherapy), except for protocol-defined pre-phase treatment, which is permitted regardless of the timing.
- ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without TBI) or boost infusion (any stem cell product; not including DLI); No evidence of graft versus host disease (GVHD) with the exception of Grade 1 skin GVHD being treated by topical treatment.
- Cellular Therapy: ≥ 28 days after the completion of DLI (donor lymphocyte infusion) or any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.).
- Understand and voluntarily provide written permission of parental/legal representative(s) to the ICF prior to conducting any trial related assessments/procedures, also concerning data and biomaterial transfer according to ICH/GCP and national/local regulations.
- Able to adhere to the trial visit schedule and other protocol requirements.
- Negative serum pregnancy tests for females of child-bearing potential within 10 days prior to treatment.
- White Blood Cell (WBC): Count must be < 25.000/µL prior to enrolment. Patients may receive cytoreduction with hydroxyurea or low-dose cytarabine (max. 100mg/m² per day) prior to enrollment.
- Patients must have a performance status ≥50% Lansky or Karnofsky score.
- Patients may have status of CNS1, CNS2, CNS3 disease without clinical signs or neurologic symptoms suggestive of CNS leukemia, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome.
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
- Patients must have adequate renal, liver and cardiac function
Exclusion Criteria
- Patients with isolated extramedullary disease.
- Hypersensitivity or allergy to the active substance or other excipients contained in the investigational medical product listed in the Summary of Product Characteristics (SmPC) or Investigators Brochure (IB).
- Patients with documented active, uncontrolled infection at the time of study entry.
- Patients with Down Syndrome.
- Patients with a secondary KMT2A-R, NPM1 or NUP98-r leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
- Patients with known partial duplication of KMT2A (MLL-PTD).
- Patients with known Mixed Lineage Leukemia.
- Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrolment.
- Patients with gastrointestinal issues of the upper gastrointestinal tract that might affect oral drug absorption.
- Patients who are currently receiving another investigational drug.
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant. Patients with active GVHD (other than Grade 1 skin GVHD).
- Patients who are receiving any strong CYP3A4 inhibitors other than itraconazole, ketoconazole, posaconazole, or voriconazole.
- Patients who are receiving any strong or moderate CYP3A4 inducers while on study or within 14 days of starting revumenib.
- Patients who are receiving medications known to prolong the QT/QTc interval (exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies, e.g, diphenhydramine, famotidine, granisetron).
- Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.
- Female patients who are pregnant or breastfeeding.
- Patients who have ever used revumenib or any other menin inhibitor.
- Female and male subjects with child bearing potential who avoid using highly effective anticonceptive measure(ment)s.
- Patients whose baseline QTcF >450ms.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 19 Feb 2026 | 2 |
 Czechia | Not Yet Recruiting | 19 Feb 2026 | 2 |
 Denmark | Recruiting | 19 Feb 2026 | 2 |
 Germany | Not Yet Recruiting | 19 Feb 2026 | 10 |
 Italy | Not Yet Recruiting | 19 Feb 2026 | 5 |
 The Netherlands | Not Yet Recruiting | 19 Feb 2026 | — |
 Poland | Not Yet Recruiting | 19 Feb 2026 | 5 |
 Sweden | Not Yet Recruiting | 19 Feb 2026 | 2 |
| Netherlands | — | — | 3 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Revumenib | Test | TABLET | ORAL | 540 | 4 | PRD11389273 |
CYTARABINE | Test | PHF00230MIG | INTRAVENOUS | 2000 | 5 | SCP142361 |
Revumenib | Test | TABLET | ORAL | 540 | 4 | PRD11389272 |
Revumenib | Test | TABLET | ORAL | 540 | 4 | PRD11389271 |
FLUDARABINE | Test | PHF00082MIG | INTRAVENOUS | 30 | 5 | SCP107125968 |
Revumenib | Test | ORAL SOLUTION | ORAL | 540 | 4 | PRD11389274 |