RecruitingRecruiting
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)
NCT04710576 · Syndax Pharmaceuticals
In plain English
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Official title
AGAVE-201, A Phase 2, Open-label, Randomized, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Axatilimab at 3 Different Doses in Patients With Recurrent or Refractory Active Chronic Graft Versus Host Disease Who Have Received at Least 2 Lines of Systemic Therapy
About this study
AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab in participants with recurrent or refractory active cGVHD after failure of at least 2 prior lines of systemic therapy due to progression of disease, intolerability, or toxicity.
Participants will be randomized to receive 1 of 3 different axatilimab treatment regimens in 28-day treatment cycles for up to 2 years.
Eligibility criteria
Inclusion Criteria:
1. Participants must be 2 years of age or older, at the time of signing the informed consent.
2. Participants who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
3. Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy.
* Refractory disease defined as meeting any of the following criteria:
* The development of 1 or more new sites of disease while being treated for cGVHD.
* Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD.
* Participants who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required.
* Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
4. Participants may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
5. Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
6. Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
7. Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
8. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
10. Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
1. Has acute GVHD without manifestations of cGVHD.
2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
3. History of acute or chronic pancreatitis.
4. History of myositis.
5. History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
6. Participants with acquired immune deficiency syndrome (AIDS).
7. Hepatitis B (defined as hepatitis B virus \[HBV\] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid \[DNA\], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C \[HCV\] antibody with positive HCV ribonucleic acid \[RNA\]).
8. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
9. Female participant who is pregnant or breastfeeding.
10. Previous exposure to CSF1-R targeted therapies.
11. Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
12. For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
13. Receiving another investigational treatment within 28 days of randomization.
14. Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).
Study design
Enrollment target: 296 participants
Allocation: randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2021-03-04
Estimated completion: 2027-09
Last updated: 2026-06-16
Interventions
Drug: Axatilimab
Primary outcomes
- • Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD) (First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks))
Sponsor
Syndax Pharmaceuticals · industry
Contacts & investigators
ContactSyndax Pharmaceuticals · contact · clinicaltrials@syndax.com · 781-419-1400
InvestigatorEllen Hooper, M.D. · study_director, Syndax Pharmaceuticals
All locations (121)
University of Alabama at Birmingham - Children's of AlabamaCompleted
Birmingham, Alabama, United States
University of Alabama at BirminghamRecruiting
Birmingham, Alabama, United States
City of HopeActive Not Recruiting
Duarte, California, United States
University of Southern California Norris Comprehensive Cancer CenterRecruiting
Los Angeles, California, United States
University of California, Los Angeles (UCLA) - Medical CenterCompleted
Los Angeles, California, United States
Stanford Cancer CenterActive Not Recruiting
Stanford, California, United States
Children's National Medical CenterActive Not Recruiting
Washington D.C., District of Columbia, United States
University of Florida (UF)Completed
Gainesville, Florida, United States
Mayo Clinic - JacksonvilleActive Not Recruiting
Jacksonville, Florida, United States
University of MiamiRecruiting
Miami, Florida, United States
AdventHealth OrlandoCompleted
Orlando, Florida, United States
MoffittActive Not Recruiting
Tampa, Florida, United States
Emory UniversityRecruiting
Atlanta, Georgia, United States
Northside HospitalActive Not Recruiting
Atlanta, Georgia, United States
The University of Chicago Medical Center (UCMC)Recruiting
Chicago, Illinois, United States
Indiana University Health Melvin and Bren Simon Cancer CenterActive Not Recruiting
Indianapolis, Indiana, United States
Franciscan Health IndianapolisCompleted
Indianapolis, Indiana, United States
Tulane University Medical CenterCompleted
New Orleans, Louisiana, United States
Johns Hopkins Kimmel Cancer CenterCompleted
Baltimore, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana Farber Cancer InstituteActive Not Recruiting
Boston, Massachusetts, United States
University of Massachusetts Memorial Medical CenterActive Not Recruiting
Worcester, Massachusetts, United States
University of MichiganActive Not Recruiting
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer InstituteRecruiting
Detroit, Michigan, United States
Henry Ford HospitalCompleted
Detroit, Michigan, United States
University of MinnesotaCompleted
Minneapolis, Minnesota, United States
Mayo Clinic - RochesterActive Not Recruiting
Rochester, Minnesota, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Rutgers Cancer Institute of New JerseyActive Not Recruiting
New Brunswick, New Jersey, United States
Weill Medical College of Cornell UniversityActive Not Recruiting
New York, New York, United States
Stony Brook University Medical CenterActive Not Recruiting
Stony Brook, New York, United States
Wake ForestCompleted
Winston-Salem, North Carolina, United States
Cincinnati Children's Hospital Medical CenterCompleted
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical CenterCompleted
Cleveland, Ohio, United States
The Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
The Cleveland Clinic FoundationActive Not Recruiting
Lyndhurst, Ohio, United States
University of Oklahoma - Health Sciences CenterActive Not Recruiting
Oklahoma City, Oklahoma, United States
Oregon Health & Science UniversityRecruiting
Portland, Oregon, United States
University of Pittsburgh Medical Center - Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical CenterActive Not Recruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterActive Not Recruiting
Houston, Texas, United States
Intermountain HealthcareRecruiting
Salt Lake City, Utah, United States
University of UtahActive Not Recruiting
Salt Lake City, Utah, United States
University of Virginia Medical CenterCompleted
Charlottesville, Virginia, United States
Fred Hutchinson Cancer Research CenterRecruiting
Seattle, Washington, United States
University of Wisconsin - Carbone Cancer CenterActive Not Recruiting
Madison, Wisconsin, United States
Froedtert Hospital and the Medical College of WisconsinActive Not Recruiting
Milwaukee, Wisconsin, United States
The Royal Children's HospitalCompleted
Parkville, Victoria, Australia
Westmead HospitalCompleted
Westmead, Australia
Universitaire Ziekenhuizen LeuvenActive Not Recruiting
Leuven, Belgium
AZ DeltaActive Not Recruiting
Roeselare, Belgium
Vancouver Coastal Health AuthorityActive Not Recruiting
Vancouver, British Columbia, Canada
Princess Margaret HospitalCompleted
Toronto, Ontario, Canada
McGill University Health Center - Research InstituteActive Not Recruiting
Montreal, Quebec, Canada
CHU Sainte-JustineActive Not Recruiting
Montreal, Quebec, Canada
CHU de GrenobleCompleted
La Tronche, Auvergne-Rhône-Alpes, France
Institut de cancérologie Strasbourg Europe (ICANS)Active Not Recruiting
Strasbourg, Grand Est, France
IUCT-OncopoleCompleted
Toulouse, Haure-Garrone, France
CHU Amiens Picardie - Hopital SudCompleted
Amiens, Hauts-de-France, France
CHRU de Lille - Hopital Claude HuriezCompleted
Lille, Hauts-de-France, France
CHRU de Nancy - Hôpitaux de BraboisCompleted
Nancy, France
CHU de Nantes - Hôtel-DieuCompleted
Nantes, France
Hopital Saint LouisCompleted
Paris, France
Hopital Pitie SalpetriereActive Not Recruiting
Paris, France
CHU Bordeaux - Hopital Haut-Leveque - Centre François MagendieActive Not Recruiting
Pessac, France
HCL Centre Hospitalier Lyon SudActive Not Recruiting
Pierre-Bénite, France
Universitaetsklinikum Carl Gustav Carus DresdenCompleted
Dresden, Germany
Universitaetsklinikum JenaCompleted
Jena, Germany
Universitaetsklinikum LeipzigCompleted
Leipzig, Germany
Universitaetsmedizin der Johannes Gutenberg - Universitaet MainzCompleted
Mainz, Germany
Universitaetsklinikum MuensterActive Not Recruiting
Münster, Germany
Universitatsklinikum RegensburgActive Not Recruiting
Regensburg, Germany
General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT UnitActive Not Recruiting
Eksochi, Thessaloniki, Greece
University Hospital of West Attica - Attikon - Hematology DivisionActive Not Recruiting
Athens, Greece
University General Hospital of PatrasCompleted
Pátrai, Greece
Rambam Health Care CampusActive Not Recruiting
Haifa, Israel
Hadassah Medical Center Ein KaremActive Not Recruiting
Jerusalem, Israel
Chaim Sheba Medical CenterActive Not Recruiting
Ramat Gan, Israel
Tel Aviv Sourasky Medical CenterActive Not Recruiting
Tel Aviv, Israel
ASST degli Spedali Civili di BresciaActive Not Recruiting
Brescia, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di MilanoCompleted
Milan, Italy
IRCCS Ospedale San RaffaeleActive Not Recruiting
Milan, Italy
ASST di Monza-Ospedale San GerardoCompleted
Monza, Italy
Fondazione Monza e Brianza per il Bambino e la sua MammaCompleted
Monza, Italy
Fondazione IRCCS Policlinico San MatteoCompleted
Pavia, Italy
Fondazione IRCCS Policlinico San MatteoCompleted
Pavia, Italy
Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro CuoreActive Not Recruiting
Roma, Italy
AOU Citta della Salute e della Scienza di Torino - Ospedale Regina MargheritaCompleted
Torino, Italy
Citta della Salute e della Scienza di Torino - Ospedale le MolinetteCompleted
Torino, Italy
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i OnkohematologiiCompleted
Gliwice, Poland
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)Completed
Lisbon, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPECompleted
Porto, Portugal
National University HospitalActive Not Recruiting
Singapore, Singapore
KK Women's and Children hospitalCompleted
Singapore, Singapore
Singapore General HospitalCompleted
Singapore, Singapore
Pusan National University HospitalActive Not Recruiting
Busan, South Korea
Korea University Anam HospitalCompleted
Seoul, South Korea
Seoul National University HospitalActive Not Recruiting
Seoul, South Korea
Severance HospitalCompleted
Seoul, South Korea
Hospital Universitario Virgen del RocioActive Not Recruiting
Seville, Seville, Spain
Hospital Universitario Vall d'HebronActive Not Recruiting
Barcelona, Spain
Hospital Clinic BarcelonaActive Not Recruiting
Barcelona, Spain
Hospital Universitario DonostiaCompleted
Donostia / San Sebastian, Spain
Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las NievesActive Not Recruiting
Granada, Spain
Hospital General Universitario Gregorio MaranonActive Not Recruiting
Madrid, Spain
Hospital Universitario Ramon y CajalCompleted
Madrid, Spain
Hospital Universitario La PazCompleted
Madrid, Spain
Hospital Universitario Puerta de HierroActive Not Recruiting
Majadahonda, Spain
Hospital Clinico Universitario de SalamancaActive Not Recruiting
Salamanca, Spain
Hospital Universitario Marquis de ValdecillaActive Not Recruiting
Santander, Spain
Hospital Clinico Universitario de ValenciaCompleted
Valencia, Spain
Hospital Universitari i Politecnic La FeActive Not Recruiting
Valencia, Spain
Kaohsiung Medical University Chung-Ho Memorial HospitalCompleted
Kaohsiung City, Taiwan
China Medical University HospitalActive Not Recruiting
Taichung, Taiwan
National Taiwan University HospitalActive Not Recruiting
Taipei, Taiwan
Bristol Royal Hospital for ChildrenCompleted
Bristol, United Kingdom
University Hospital of WalesActive Not Recruiting
Cardiff, United Kingdom
Queen Elizabeth University HospitalCompleted
Glasgow, United Kingdom
Hammersmith HospitalActive Not Recruiting
London, United Kingdom
King's College Hospital NHS Foundation TrustActive Not Recruiting
London, United Kingdom
Royal Marsden Foundation TrustCompleted
London, United Kingdom