Phase III study of revumenib in combination with intensive chemotherapy in newly diagnosed NPM1-mutated AML

ISRCTN ISRCTN42617850
DOI https://doi.org/10.1186/ISRCTN42617850
ClinicalTrials.gov (NCT) NCT07211958
Clinical Trials Information System (CTIS) Nil known
Integrated Research Application System (IRAS) 1012542
Protocol serial number SNDX-5613-0710
Sponsor Syndax Pharmaceuticals, Inc.
Funder Syndax Pharmaceuticals
Submission date
24/10/2025
Registration date
06/02/2026
Last edited
06/02/2026
Recruitment status
Not yet recruiting
Overall study status
Ongoing
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
This study aims to determine if adding a drug called revumenib to standard chemotherapy can improve outcomes for patients with newly diagnosed acute myeloid leukemia (AML) that has a specific genetic mutation called NPM1. AML is an aggressive blood cancer, and while current treatments can lead to remission, many patients still relapse. This research is important because it could potentially lead to a more effective first-line treatment for this type of AML.
The study will test revumenib, an oral medication that targets a specific protein interaction involved in AML development. The use of revumenib in this study is investigational, which means that revumenib is not approved by any regulatory authorities for this indication.

Who can participate?
Participants aged 12 years and older with newly diagnosed NPM1-mutated AML who are eligible for intensive chemotherapy

What does the study involve?
Participants will be randomly assigned to receive either revumenib or a placebo along with standard chemotherapy. Neither participants nor doctors will know who receives revumenib versus placebo. Patients will undergo regular blood tests, bone marrow biopsies, imaging scans and other assessments to monitor their response to treatment and any side effects.

What are the possible benefits and risks of participating?
There is no guarantee that taking part in this study will improve participants’ health and it is possible that their condition may get worse. However, participants will contribute to important research that could improve treatment options for AML.
Due to the character count limit for this question it is not possible to add the full list of potential risks and burdens. Please see the following sections of the Main Participant Information Sheet and Informed Consent Form for a full list of potential risks and burdens: "What side effects or risks can I expect from being in the study?" and "Risks Associated with the Study Tests and Procedures".

Where is the study run from?
Syndax Pharmaceuticals, Inc. (USA)

When is the study starting and how long is it expected to run for?
October 2025 to January 2031

Who is funding the study?
Syndax Pharmaceuticals, Inc. (USA)

Who is the main contact?
clinicaltrials@syndax.com

Contact information

Syndax Pharmaceuticals
Scientific

730 3rd Avenue Floor 9
New York
10017-3206
United States of America

+1 (0)781 419 1400
clinicaltrials@syndax.com
Dr David Taussig
Principal investigator

Downs Road
Sutton
SM2 5PT
United Kingdom

+44 (0)20 86613655
david.taussig@rmh.nhs.uk

Study information

Primary study designInterventional
Study designDouble-blind randomized placebo-controlled trial
Secondary study designRandomised controlled trial
Scientific titleA Phase III, randomized, double-blind, placebo-controlled study of revumenib in combination with intensive chemotherapy in participants with newly diagnosed AML with an NPM1 mutation (REVEAL-ND NPM1)
Study acronymREVEAL-ND NPM1
Study objectivesPrimary objectives:
1. To evaluate if revumenib + IC improves EFS compared to placebo + IC
2. To evaluate if revumenib + IC improves MRDBM (-) CR rate, compared to placebo + IC

Secondary objectives:
1. To evaluate if revumenib + IC improves OS compared to placebo + IC
2. To evaluate if revumenib + IC improves EFS compared to placebo + IC
3. To evaluate if revumenib + IC improves MRDBM (-) CR rate compared to placebo + IC
4. To evaluate the MRDPB (-) CR rate for revumenib + IC compared to placebo + IC
5. To evaluate the MRDBM (-) CR rate for revumenib + IC compared to placebo + IC
6. To evaluate if revumenib in combination with IC improves CR rate compared to placebo + IC
7. To evaluate CRc rate for revumenib + IC compared to placebo + IC
8. To evaluate ORR in revumenib + IC compared to placebo + IC
9. To evaluate duration of CR for revumenib + IC compared to placebo + IC
10. To evaluate duration of CRc for revumenib + IC compared to placebo + IC
11. To evaluate DOR for revumenib + IC compared to placebo + IC
12. To evaluate the safety and tolerability of revumenib + IC compared to placebo + IC
13. To evaluate patient-reported fatigue for revumenib + IC compared to placebo + IC
Ethics approval(s)

Approved 11/12/2025, London - Brighton & Sussex Research Ethics Committee (2 Redman Place, Stratford, London, E20 1QJ, United Kingdom; -; brightonandsussex.rec@hra.nhs.uk), ref: 25/LO/0831

Health condition(s) or problem(s) studiedNewly diagnosed acute myeloid leukemia (AML) with an NPM1 mutation
InterventionExperimental Arm: Revumenib + Intensive Chemotherapy (IC). Participants will receive revumenib orally plus an IC regimen of cytarabine and danorubicin by intravenous (IV) infusion.
Placebo Comparator: Placebo + IC. Participants will receive placebo (non-active agent) orally plus and IC regimen of cytarabine and danorubicin by IV.

Please note that the dose range, frequency and randomisation process are considered CCI and cannot be disclosed.
Intervention typeDrug
PhasePhase III
Drug / device / biological / vaccine name(s)Revumenib, cytarabine, daunorubicin, idarubicin
Primary outcome measure(s)

1. Event-Free Survival (EFS): Defined as the time from the date of randomization to the date of induction treatment failure, relapse, or death due to any cause, whichever occurs first. Time frame up to 2 years.
2. Minimal Residual Disease in Bone Marrow Negative Complete Response Rate (MRDBM- CR rate): Defined as the percentage of participants with Complete Response (CR) (IRC-assessed). Time frame up to 2 years.

Key secondary outcome measure(s)

1. Overall Survival (OS): Defined as the time from the date of randomization to the date of death from any cause. Time frame up to 5 years.
2. Event-Free Survival (EFS, Investigator-assessed): Defined as the time from the date of randomization to the date of Induction treatment failure, relapse or death due to any cause, whichever occurs first. Time frame up to 2 years.
3. Minimal Residual Disease in Bone Marrow Negative Complete Response Rate (MRDBM- CR rate, molecular assay): Defined as the percentage of participants with CR (Investigator-assessed) who achieve MRDBM (-) status by molecular assay. Time frame up to 2 years.
4. Minimal Residual Disease in Peripheral Blood Negative Complete Response Rate (MRDPB- CR rate, molecular assay): Defined as the percent of participants with CR (Investigator-assessed) who achieve MRDPB (-) status by molecular assay. Time frame up to 2 years.
5. Minimal Residual Disease in Bone Marrow Negative Complete Response Rate (MRDBM- CR rate, flow cytometry): Defined as the percent of participants with CR who achieve MRDBM (-) status by flow cytometry after Induction and/or Consolidation. Time frame up to 2 years.
6. Complete Response Rate (CR rate, Investigator-assessed): Defined as the percentage of participants who achieve CR. Time frame up to 2 years.
7. Composite Complete Response Rate (CRc rate, Investigator-assessed): Defined as the rate of CR + CRh + CRi. Time frame up to 2 years.
8. Overall Response Rate (ORR, Investigator-assessed): Defined as the rate of CR + CRh + CRi + MLFS + PR. Time frame up to 2 years.
9. Duration of Complete Response (Duration of CR): Defined as time from first date of first CR to relapse or death. Time frame up to 2 years.
10. Duration of Composite Complete Response (Duration of CRc): Defined as time from date of first CRc to relapse or death. Time frame up to 2 years.
11. Duration of Response (DOR): Defined as time from date of first documented response (CR, CRh, CRi, PR, or MLFS) to the first documented relapse or death. Time frame up to 2 years.
12. Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs): Frequency, duration, and severity. Time frame up to 2 years.
13. Clinical Laboratory Abnormalities: Incidence and shifts from baseline of clinically significant clinical laboratory abnormalities. Time frame up to 2 years.
14. Other Safety Observations: Change from baseline in ECGs, vital signs, and performance status. Time frame up to 2 years.

Completion date01/01/2031

Eligibility

Participant type(s)Patient
Age groupMixed
Lower age limit12 Years
Upper age limit110 Years
SexAll
Target sample size at registration468
Key inclusion criteria1. Participants must have newly diagnosed and previously untreated AML and be candidates for intensive chemotherapy
2. Presence of an NPM1 mutation
3. Eastern Cooperative Oncology Group performance status ≤2 (≤1 if >65 years old); Karnofsky or Lansky ≥40
4. Have a life expectancy of ≥3 months as judged by the Investigator
5. Negative serum pregnancy test
6. Adequate liver, kidney, and cardiac function
Key exclusion criteria1. Diagnosis of active acute promyelocytic leukemia
2. Active central nervous system disease
3. Fridericia's corrected QT interval (QTcF) >450 milliseconds at screening, diagnosis or suspicion of Long QT syndrome or family history of Long QT syndrome
4. Any gastrointestinal (GI) issue of the upper GI tract likely to affect oral drug absorption or ingestion
5. Any concurrent malignancy requiring active therapy (except breast or prostate cancer stable on or responding to endocrine therapy)
6. Inability to swallow oral medication
7. Pregnant or nursing females
8. Participant has known active or chronic hepatitis B or active hepatitis C (HCV) infection or human immunodeficiency virus (HIV)-positive with detectable viral load
Date of first enrolment16/03/2026
Date of final enrolment30/11/2027

Locations

Countries of recruitment

  • United Kingdom
  • England
  • Northern Ireland
  • Scotland

Study participating centres

The Royal Marsden NHS Foundation Trust
Fulham Road
London
SW3 6JJ
England
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Aberdeen Royal Infirmary
Foresterhill Road
Aberdeen
AB25 2ZN
Scotland
Imperial College Healthcare NHS Trust
The Bays
St Marys Hospital
South Wharf Road
London
W2 1BL
England
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
England
University Hospital Southampton NHS Foundation Trust
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
England
Belfast Health and Social Care Trust
Trust Headquarters
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
Northern Ireland
United Lincolnshire Teaching Hospitals NHS Trust
Lincoln County Hospital
Greetwell Road
Lincoln
LN2 5QY
England
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
Scotland
University Hospitals of Derby and Burton NHS Foundation Trust
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
England

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
IPD sharing plan

Editorial Notes

24/12/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 24/12/2025
24/10/2025: Study's existence confirmed by the HRA.

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