Revumenib Treatment in Combination with FLA Chemotherapy in Paediatric Refractory/Relapsed KMT2A-r, NUP98-r or NPM1-mut Acute Myeloid Leukemia (AML)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pediatric Research International GmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-02-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Syndax Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To estimate the overall response rate (ORR) according to pediatric specific response criteria (Ped- morph-CR/CRi/CRp) after up to 2 cycles with revumenib in combination with FLA in patients with refractory/relapsed (R/R) KMT2A-r, NUP98-r or NPM1-mut AML

Secondary objectives 5

1. To collect biomaterials that can be used for biological sub-studies subsequently conducted in this patient population of the clinical trial
2. To describe the PopPK parameters of revumenib and its primary metabolite (M1), in combination with FLA in patients with R/R KMT2A-r, NUP98-r or NPM1- mutated AML
3. To describe the hematopoietic stem cells transplant (HSCT) rate in patients with R/R KMT2A-r, NUP98-r or NPM1-mut AML after up to 2 cycles of revumenib in combination with FLA.
4. To estimate the overall survival rate in patients treated with revumenib.
5. To evaluate the safety and toxicity of the study treatment.

Conditions and MedDRA coding

Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients must be > 30 days and ≤ 18 years of age at time of enrollment.
2. 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).
3. ≥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.
4. ≥ 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.
5. 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.).
6. 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.
7. Able to adhere to the trial visit schedule and other protocol requirements.
8. Negative serum pregnancy tests for females of child-bearing potential within 10 days prior to treatment.
9. 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.
10. Patients must have a performance status ≥50% Lansky or Karnofsky score.
11. 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.
12. Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
13. Patients must have adequate renal, liver and cardiac function

Exclusion criteria 19

1. Patients with isolated extramedullary disease.
2. 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).
3. Patients with documented active, uncontrolled infection at the time of study entry.
4. Patients with Down Syndrome.
5. Patients with a secondary KMT2A-R, NPM1 or NUP98-r leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
6. Patients with known partial duplication of KMT2A (MLL-PTD).
7. Patients with known Mixed Lineage Leukemia.
8. Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrolment.
9. Patients with gastrointestinal issues of the upper gastrointestinal tract that might affect oral drug absorption.
10. Patients who are currently receiving another investigational drug.
11. 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).
12. Patients who are receiving any strong CYP3A4 inhibitors other than itraconazole, ketoconazole, posaconazole, or voriconazole.
13. Patients who are receiving any strong or moderate CYP3A4 inducers while on study or within 14 days of starting revumenib.
14. 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).
15. 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.
16. Female patients who are pregnant or breastfeeding.
17. Patients who have ever used revumenib or any other menin inhibitor.
18. Female and male subjects with child bearing potential who avoid using highly effective anticonceptive measure(ment)s.
19. Patients whose baseline QTcF >450ms.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint of Part I in this study is to estimate the ORR. We will compare the ORR to a historically informed null ORR rate of 37% after up to 2 cycles with revumenib in combination with FLA in R/R KMT2A-r, NUP98-r or NPM1- mut AML.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pediatric Research International GmbH

Sponsor organisation

Pediatric Research International GmbH

Address

Freiheit 1, Suedviertel Suedviertel

City

Essen

Postcode

45128

Country

Germany

Scientific contact point

Organisation

Pediatric Research International GmbH

Contact name

Kristian Juul-Dam, MD, PhD

Public contact point

Organisation

Pediatric Research International GmbH

Contact name

Katarzyna Majstrowicz, PhD

Third parties 7

Locations

8 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications