Acute Myeloid LeukemiaPhase 1/2AUGMENT-101NCT04065399
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation
A Phase 1/2 study testing revumenib and cobicistat in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Syndax Pharmaceuticals at 57 sites in 11 countries.
Trial summary
Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia. In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of… Read more about this study
- Who is it for?
- Ages 30 days and older
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Lineage Acute Leukemia
- What is being tested?
- revumenib and cobicistat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 447 participants
- Where
- 57 sitesin 11 countries
- Study dates
- 5 Nov 2019to 15 Dec 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants must have active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.
- Phase 1:
- Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
- Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
- Arm C: Participants receiving revumenib in combination with cobicistat.
- Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
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- Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
- Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
- Phase 2:
- Documented R/R active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the NCCN Guidelines® for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
- Cohort 2A: Documented R/R ALL/MPAL with KMT2A rearrangement.
- Cohort 2B: Documented R/R AML with KMT2A rearrangement.
- Cohort 2C: Documented R/R AML with NPM1m.
- Cohort 2D: Documented R/R acute leukemia with a genetic mutation expected to lead to HOX/MEIS upregulation (for example, KMT2Ar, NPM1m, and NUP98r), including participants who are MRD-positive by multiparametric flow cytometry or molecular methods only, and including participants with isolated extramedullary disease.
- White blood cell count below 25,000/ microliter at time of enrollment. Participants may receive cytoreduction prior to enrollment per protocol-specified criteria.
- Male or female participants aged ≥30 days old. Participants intended to receive SNDX-5613 in combination with cobicistat must weigh ≥35 kilograms (kg). Participants in Cohort 2D must be ≥18 years of age and have a body weight ≥40 kg.
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥50.
- Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia.
- Phase 1 and Phase 2 Cohorts 2A-2C only:
- Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
- Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
- Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T or NK cell therapy.
- Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy.
- Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
- Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
- Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing or cytoreductive therapy.
- Phase 2 Cohort 2D only:
- At least 14 days since any other investigational or commercially available antileukemic therapy, with the following exceptions:
- Cytoreductive therapy with hydroxyurea, low-dose cytarabine (20 mg/square meter (m^2)/day subcutaneously [SC] for 10 days) or low-dose etoposide (up to 200 mg/day orally for 10 days) may be administered concurrently with SNDX-5613.
- Intrathecal chemotherapy for CNS prophylaxis is permitted at the treating physician's discretion.
- Steroids at physiologic dosing (equivalent to ≤10 mg prednisone daily for participants ≥18 years or ≤10 mg/m^2/day for participants <18 years) or for cytoreductive therapy.
- Adequate organ function.
- If of childbearing potential, willing to use a highly effective method of contraception from the time of enrollment through 120 days following the last study drug dose.
Who cannot join
- Participants meeting any of the following criteria are not eligible for study participation:
- Diagnosis of active acute promyelocytic leukemia.
- Isolated extramedullary relapse (Phase 2 Cohorts 2A-2C only).
- Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
- Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
- Hepatitis B or C.
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- Pregnant or nursing women.
- Cardiac Disease:
- Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
- Corrected QT interval (QTc) >450 milliseconds.
- Gastrointestinal Disease:
- any gastrointestinal issue of the upper GI tract that might affect oral drug absorption or ingestion (that is, gastric bypass and gastroparesis).
- Cirrhosis with a Child-Pugh score of B or C.
- Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
- Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the participant is not receiving any systemic therapy or radiation.
- In Phase 1 and Phase 2: Participants requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (for example, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1 and in Phase 2.
- Note: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
57 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
57 sites in 11 countries
United States22 sites, 10 recruiting
- Recruiting
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
Feranmi Arowolo, feranmi.arowolo@emory.edu
Martha Arellano
- Completed
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
- Recruiting
University of Colorado
Aurora, Colorado, 80045
Katelyn Anttila, Katelyn.Anttila@ucdenver.edu
Christine McMahon
- Active, not recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
The University of Chicago Medical Center
Chicago, Illinois, 60637
Bukola Rinola, 773-795-2430, Bukola.Rinola@bsd.uchicago.edu
Michael Thirman
- Completed
University of Cincinnati
Cincinnati, Ohio, 45267
- Recruiting
Ohio State University
Columbus, Ohio, 43201
Mandana Moghaddam, 614-685-2932, Mandana.Moghaddam@osumc.edu
James Blachly
- Active, not recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27110
Linda Brown, linda.brown@duke.edu
Brittany DePriest
- Completed
Hackensack University Medical Center
Hackensack, New Jersey, 07601
- Active, not recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
University of Iowa Hospital
Iowa City, Iowa, 52246
Chris Stamy, 319-467-5320, chris-stamy@uiowa.edu
Michael Halyko
- Completed
University Of California Care Medical Group - Norris Comprehensive Cancer Center And Hospital
Los Angeles, California, 90033
- Active, not recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
Montefiore Medical Center
New York, New York, 10467
Aradhika Dhawan, aradhika.dhawan@einsteinmed.edu
Ioannis Mantzaris
- Active, not recruiting
Stanford Cancer Institute
Palo Alto, California, 94305
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Robin E Blauser, BSN RN, 215-662-2870, Robin.Blauser@pennmedicine.upenn.edu
Thomas Greenwood, Thomas.Greenwood@Pennmedicine.upenn.edu
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
Tess Messan, 503-494-5466, Allentes@ohsu.edu
Elie Traer, MD
- Completed
Huntsman Cancer Institute at the University of Utah
Salt Lake City, Utah, 84112
- Active, not recruiting
Florida Cancer Specialists and Research Institute
Sarasota, Florida, 34232
- Recruiting
Washington University in St. Louis School of Medicine
St Louis, Missouri, 63110
Morgan Swanner, swanner@wustl.edu
John DiPersio
- Completed
Moffitt Cancer Center
Tampa, Florida, 33162
Germany7 sites, 4 recruiting
- Withdrawn
Universitaetsklinikum Essen (AoR)
Essen, 45147
- Completed
Universitaetsmedizin Greifswald
Greifswald, 17475
- Recruiting
Universitaetsmedizin Der Johannes
Gutenberg, 55131
m3.uct-studien@unimedizin-mainz.de
- Recruiting
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
Petra Kuehne, p.kuehne@uke.de
Franziska Westendorf
- Recruiting
University of Leipzig
Leipzig, 04103
Karolin Neelsen, karolin.neelsen@medizin.uni-leipzig.de
Madlen Jentzsch
- Completed
Klinikum Nuernberg Nord
Nuremberg, 90419
- Recruiting
University Hospital Of Ulm, Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Christiane Rudolph, +49 (0)731 500 45903, Christiane.Rudolph@uniklinik-ulm.de
Hartmut Doehner
Israel6 sites, 6 recruiting
- Recruiting
Rambam Health Care Campus (RHCC)
Haifa, 3109601
Lareen Bouban, l_boban@rambam.health.gov.il
Avraham Frisch
- Recruiting
Shaare Zedek Medical Center
Jerusalem, 9103102
Razan Ewisat, razanew@szmc.org.il
Yishai Ofran
- Recruiting
Hadassah Medical Center- Ein Kerem
Jerusalem, 9112001
Leah Greenfeld
leahgr@hadassah.org.il
- Recruiting
Galilee Medical Center
Nahariya, 2210010
Lana Saada, LanaS@gmc.gov.il
Galia Stemer
- Recruiting
Rabin Medical Center
Petah Tikva, 4941492
Shani Gillows, shanigil@clalit.org.il
Ofir Wolach
- Recruiting
Sheba Medical Center
Ramat Gan, 52621
Yuval Carmel, Yuval.Carmel@sheba.health.gov.il
Irina Armitai
Australia5 sites, 3 recruiting
- Active, not recruiting
Peter MacCallum Cancer Centre (PMCC)
Melbourne, Victoria, 3000
- Recruiting
Alfred Hospital
Melbourne, 3004
Shaun Fleming, MD
- Recruiting
Sir Charles Gairdner Hospital
Nedlands, 6009
Carolyn Grove, MD
- Active, not recruiting
Royal Melbourne Hospital (RMH)
Parkville, Victoria, 3050
- Recruiting
Royal North Shore Hospital
Saint Leonards, 2065
Matthew Greenwood, MD
Italy5 sites, 5 recruiting
- Recruiting
IRCCS Azienda Ospedaliero Universitaria di Bologna
Bologna, 40138
Riccardo Mennuti, riccardo.mennuti@aosp.bo.it
Cristina Papayannidis
- Recruiting
Istituto Romagnolo Per Lo Studio dei tumori Dino Amadori
Meldola, 47014
Fabiana Mammoli, fabiana.mammoli@irst.emr.it
Maria Giannini
- Recruiting
IRCCS-Istituto Europeo di Oncologia
Milan, 20141
Marialuisa Catalano, Marialuisa.Catalano@ieo.it
Enrico Derenzini
- Recruiting
Universita Cattolica Fondazione Policlinico Agostino Gemelli
Roma, 00168
Gulia De Santis, giulia.desantis@policlinicogemelli.it
Patrizia Chiusolo
- Recruiting
S Bortolo Hospital AULSS 8 Berica
Vicenza, 36100
Irene Mutterle, irene.mutterle@aulss.veneto.it
Giorgia Scotton
France4 sites, 4 recruiting
- Recruiting
Hospital Saint-Louis - APHP
Paris, 75010
Marion Le Duff, marion.leduff@aphp.fr
Emmanuel Raffoux
- Recruiting
Centre Hospitalier Universitaire (CHU) de Bordeaux
Pessac, 33604
Thomas Grenier, thomas.grenier@chu-bordeaux.fr
Arnaud Pigneux
- Recruiting
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
James EAV, ext-james.eav@chu-lyon.fr
Mael Heiblig
- Recruiting
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
Villejuif, 94805
Laetitia PIREYRE, Laetitia.PIREYRE@gustaveroussy.fr
Stephanie De Botton
Spain3 sites, 3 recruiting
- Recruiting
Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908
Alvaro Gonzalez, amayo@idibell.cat
Montserrat Arnan Sangerman
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, 41013
Laura More, lauramorahuvr@gmail.com
Eduardo Rodriguez-Arboli
- Recruiting
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Alvaro Fernandez-Pardo, alvaro_fernandez@iislafe.es
Pau Montesinos Fernandez
Canada2 sites, 1 recruiting
- Recruiting
University Health Network
Toronto, M5G 2M9
Allison Mahon, Allison.Mahon@uhn.ca
Andre Schuh, MD
- Active, not recruiting
The Hospital for Sick Children
Toronto
Lithuania1 site, 1 recruiting
- Recruiting
Vilnius University Hospital Santaros Klinikos
Vilnius, 08661
Busevicius Mingaudas, mingaudas.busevicius@santa.lt
Andrius Zucenka
Netherlands1 site, 1 recruiting
- Not yet recruiting
Princess Maxima Center for Pediatric Oncology
Utrecht, 3584 CS
Secretary Trial and Data Centrum, tdcsecretary@prinsesmaximacentrum.nl
Michael Zwaan
Puerto Rico1 site, 1 recruiting
- Recruiting
Hospital Centro Comprensivo de Cancer UPR
San Juan, 00935
Coral Del Mar Lázaga Ocasio Ocasio, clazaga@cccupr.org
Alexis Cruz-Chacon
About this study
Official title: A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation
Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia.
In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.
Read the detailed description
Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms:
Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole.
Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
Arm C: Participants receiving revumenib and cobicistat.
Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib:
- Cohort 2A: Participants with KMT2Ar acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL)
- Cohort 2B: Participants with KMT2A AML
- Cohort 2C: Participants with NPM1m AML
- Cohort 2D: Participants with acute leukemia (including KMT2Ar, NPM1m, NUP98r and other acute leukemias expected to have HOX/MEIS upregulation)
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Lineage Acute Leukemia, Mixed Phenotype Acute Leukemia, Acute Leukemia of Ambiguous Lineage
- Being tested
- revumenib, cobicistat
- Keywords
- AML, ALL, MPAL, MLAL, ALAL, relapsed leukemia, refractory leukemia, acute leukemia, KMT2A, NPM1
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
revumenibDrug
Also called SNDX-5613
revumenib orally
cobicistatDrug
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
| Study group | Role | What they receive |
|---|---|---|
| Revumenib | Experimental | Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib. Participants will be enrolled in 1 of 6 dose-escalation arms:
* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole
* Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis
* Arm C: Participants receiving revumenib and cobicistat
* Arm D: Participants receiving fluconazole for antifungal prophylaxis
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers
* Arm F: Participants receiving isavuconazole for antifungal prophylaxis
Phase 2: Oral revumenib; 4 indication-specific expansion cohorts will be enrolled:
* Cohort 2A: Participants with KMT2Ar ALL/MPAL
* Cohort 2B: Participants with KMT2Ar AML
* Cohort 2C: Participants with NPM1m AML
* Cohort 2D: Participants with acute leukemia (including KMT2Ar, NPM1m, NUP98r and other acute leukemias expected to have HOX/MEIS upregulation) Receives: Drug: revumenib; Drug: cobicistat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose-limiting toxicities (DLTs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Measured: Approximately 1 year
Number of participants with treatment-emergent adverse events (TEAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Measured: Approximately 1 year
Cmax (Phase 1)
Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)
Measured: Approximately 1 year
Tmax (Phase 1)
Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)
Measured: Approximately 1 year
AUC0-t (Phase 1)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of revumenib and relevant metabolites (Phase 1)
Measured: Approximately 1 year
CR+CRh rate (Phase 2 [Cohorts 2A-2C])
To assess the complete remission (CR) and complete remission with partial hematologic recovery (CRh) rate (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
Number of participants with TEAEs (Phase 2 [Cohorts 2A-2C])
Assessed by the NCI CTCAE version 5.0 (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
Cmax (Phase 2 [Cohort 2D])
Cmax of revumenib (Phase 2 [Cohort 2D])
Measured: Approximately 3 years
AUC0-tau (Phase 2 [Cohort 2D])
Area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau) of revumenib (Phase 2 [Cohort 2D])
Measured: Approximately 3 years
Secondary outcomes (11)
Transfusion independence (Phase 2 [Cohorts 2A-2C])
Transfusion independence is defined as any transfusion-free period lasting for at least 56 consecutive days
Measured: Approximately 3 years
CRc rate (Phase 2 [Cohorts 2A-2C])
To assess the composite definition of complete remission (CRc) rate (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
ORR (CRc+ morphological leukemia-free state [MLFS] + partial remission [PR]) (Phase 2 [Cohorts 2A-2C])
To assess the overall response rate (ORR) of revumenib (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
TTR (Phase 2 [Cohorts 2A-2C])
To assess the time to response (TTR) of revumenib (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 34 months
DOR (Phase 2 [Cohorts 2A-2C])
To assess the duration of response (DOR) of revumenib (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
EFS (Phase 2 [Cohorts 2A-2C])
To assess the event free survival (EFS) of revumenib (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
OS (Phase 2 [Cohorts 2A-2C])
To assess overall survival (OS) of revumenib (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 5 years
Cmax (Phase 2 [Cohorts 2A-2C])
Cmax of revumenib and relevant metabolites (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
Tmax (Phase 2 [Cohorts 2A-2C])
Tmax of revumenib and relevant metabolites (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
AUC0-t (Phase 2 [Cohorts 2A-2C])
AUC0-t of revumenib and relevant metabolites (Phase 2 [Cohorts 2A-2C])
Measured: Approximately 3 years
Number of participants with TEAEs (Phase 2 [Cohort 2D])
Assessed by the NCI CTCAE version 5.0 (Phase 2 [Cohort 2D]))
Measured: Approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2019
- Study start5 Nov 2019
- Primary completion15 Dec 2027 (estimated)
- Study completion15 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Phase 1 will employ an accelerated titration design. The dose escalation will follow a modified Fibonacci sequence.
- Masking
- None (open label)
- Enrolment
- 447 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Angela R Smith, M.D., Study director, Syndax Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04065399
- Sponsor's protocol ID
- SNDX-5613-0700
- Other IDs
- 2020-004104-34
- Acronym
- AUGMENT-101
- Status last verified
- Oct 2026
- First submitted
- 16 Aug 2019
- Last updated
- 9 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Garcia MB, Wang B, Sheikh I, El Hajjar G, McCall D, Nunez C, Gibson A, Lorenzi PL, Issa GC, Cuglievan B, Abbas HA. High-Throughput Proteomic Profiling to Evaluate Differentiation Syndrome With Menin Inhibition. Mol Cell Proteomics. 2026 Mar;25(3):101522. doi: 10.1016/j.mcpro.2026.101522. Epub 2026 Jan 30.
PubMed 41621809Arellano ML, Thirman MJ, DiPersio JF, Heiblig M, Stein EM, Schuh AC, Zucenka A, de Botton S, Grove CS, Mannis GN, Papayannidis C, Perl AE, Issa GC, Aldoss I, Bajel A, Dickens DS, Kuhn MWM, Mantzaris I, Raffoux E, Traer E, Amitai I, Dohner H, Greco C, Kovacsovics T, McMahon CM, Montesinos P, Pigneux A, Shami PJ, Stone RM, Wolach O, Harpel JG, Chudnovsky Y, Yu L, Bagley RG, Smith AR, Blachly JS. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025 Aug 28;146(9):1065-1077. doi: 10.1182/blood.2025028357.
PubMed 40332046Issa GC, Aldoss I, Thirman MJ, DiPersio J, Arellano M, Blachly JS, Mannis GN, Perl A, Dickens DS, McMahon CM, Traer E, Zwaan CM, Grove CS, Stone R, Shami PJ, Mantzaris I, Greenwood M, Shukla N, Cuglievan B, Kovacsovics T, Gu Y, Bagley RG, Madigan K, Chudnovsky Y, Nguyen HV, McNeer N, Stein EM. Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). J Clin Oncol. 2025 Jan;43(1):75-84. doi: 10.1200/JCO.24.00826. Epub 2024 Aug 9.
PubMed 39121437Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, Thirman MJ, Patel MR, Dickens DS, Shenoy S, Shukla N, Kantarjian H, Armstrong SA, Perner F, Perry JA, Rosen G, Bagley RG, Meyers ML, Ordentlich P, Gu Y, Kumar V, Smith S, McGeehan GM, Stein EM. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023 Mar;615(7954):920-924. doi: 10.1038/s41586-023-05812-3. Epub 2023 Mar 15.
PubMed 36922593Sasca D, Guezguez B, Kuhn MWM. Next generation epigenetic modulators to target myeloid neoplasms. Curr Opin Hematol. 2021 Sep 1;28(5):356-363. doi: 10.1097/MOH.0000000000000673.
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