Chronic Graft-versus-host-diseasePhase 2AGAVE-201NCT04710576
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)
A Phase 2 study testing Axatilimab in people with Chronic Graft-versus-host-disease, run by Syndax Pharmaceuticals at 121 sites in 16 countries.
Trial summary
This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Chronic Graft-versus-host-disease
- What is being tested?
- Axatilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 296 participants
- Where
- 121 sitesin 16 countries
- Study dates
- 4 Mar 2021to Sep 2027
- Phase
- Phase 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants must be 2 years of age or older, at the time of signing the informed consent.
- 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.
- 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.
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- 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.
- 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.
- Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged <16 years)
- Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
- Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- 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.
- Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
- 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.
Who cannot join
- Participants are excluded from the study if any of the following criteria apply:
- Has acute GVHD without manifestations of cGVHD.
- Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
- History of acute or chronic pancreatitis.
- History of myositis.
- 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.
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- Participants with acquired immune deficiency syndrome (AIDS).
- 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]).
- 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).
- Female participant who is pregnant or breastfeeding.
- Previous exposure to CSF1-R targeted therapies.
- Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
- 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.
- Receiving another investigational treatment within 28 days of randomization.
- 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).
Trial locations and contacts
121 sites in 16 countries. Contact the study team or a site near you to ask about taking part.
121 sites in 16 countries
United States47 sites, 13 recruiting
- Active, not recruiting
University of Michigan
Ann Arbor, Michigan, 48084
- Recruiting
Emory University
Atlanta, Georgia, 30322
- Active, not recruiting
Northside Hospital
Atlanta, Georgia, 30342
- Completed
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, 21231-2410
- Completed
University of Alabama at Birmingham - Children's of Alabama
Birmingham, Alabama, 35233
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Active, not recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Completed
University of Virginia Medical Center
Charlottesville, Virginia, 22908
- Recruiting
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637
- Completed
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
- Completed
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
- Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
- Completed
Henry Ford Hospital
Detroit, Michigan, 48202
- Active, not recruiting
City of Hope
Duarte, California, 91010
- Completed
University of Florida (UF)
Gainesville, Florida, 32610
- Active, not recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Active, not recruiting
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
- Completed
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237
- Active, not recruiting
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
- Recruiting
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033
- Completed
University of California, Los Angeles (UCLA) - Medical Center
Los Angeles, California, 90059
- Active, not recruiting
The Cleveland Clinic Foundation
Lyndhurst, Ohio, 44195
- Active, not recruiting
University of Wisconsin - Carbone Cancer Center
Madison, Wisconsin, 53792
- Recruiting
University of Miami
Miami, Florida, 33136
- Active, not recruiting
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Completed
University of Minnesota
Minneapolis, Minnesota, 55455
- Active, not recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Active, not recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
- Completed
Tulane University Medical Center
New Orleans, Louisiana, 70112
- Active, not recruiting
Weill Medical College of Cornell University
New York, New York, 10022
- Active, not recruiting
University of Oklahoma - Health Sciences Center
Oklahoma City, Oklahoma, 73104
- Completed
AdventHealth Orlando
Orlando, Florida, 32806
- Recruiting
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
- Active, not recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
- Recruiting
Intermountain Healthcare
Salt Lake City, Utah, 84111
- Active, not recruiting
University of Utah
Salt Lake City, Utah, 84112
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Active, not recruiting
Stanford Cancer Center
Stanford, California, 94305
- Active, not recruiting
Stony Brook University Medical Center
Stony Brook, New York, 11794
- Active, not recruiting
Moffitt
Tampa, Florida, 33612
- Active, not recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
- Completed
Wake Forest
Winston-Salem, North Carolina, 27157
- Active, not recruiting
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655
Spain13 sites
- Active, not recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
- Active, not recruiting
Hospital Clinic Barcelona
Barcelona, 8032
- Completed
Hospital Universitario Donostia
Donostia / San Sebastian
- Active, not recruiting
Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves
Granada, 18014
- Active, not recruiting
Hospital General Universitario Gregorio Maranon
Madrid, 28007
- Completed
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Completed
Hospital Universitario La Paz
Madrid, 28046
- Active, not recruiting
Hospital Universitario Puerta de Hierro
Majadahonda
- Active, not recruiting
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
- Active, not recruiting
Hospital Universitario Marquis de Valdecilla
Santander
- Active, not recruiting
Hospital Universitario Virgen del Rocio
Seville, Seville, 41013
- Completed
Hospital Clinico Universitario de Valencia
Valencia, 46010
- Active, not recruiting
Hospital Universitari i Politecnic La Fe
Valencia, 46026
France11 sites
- Completed
CHU Amiens Picardie - Hopital Sud
Amiens, Hauts-de-France, 80054
- Completed
CHU de Grenoble
La Tronche, Auvergne-Rhône-Alpes, 38700
- Completed
CHRU de Lille - Hopital Claude Huriez
Lille, Hauts-de-France, 59037
- Completed
CHRU de Nancy - Hôpitaux de Brabois
Nancy
- Completed
CHU de Nantes - Hôtel-Dieu
Nantes
- Completed
Hopital Saint Louis
Paris, 75010
- Active, not recruiting
Hopital Pitie Salpetriere
Paris, 75013
- Active, not recruiting
CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie
Pessac
- Active, not recruiting
HCL Centre Hospitalier Lyon Sud
Pierre-Bénite
- Active, not recruiting
Institut de cancérologie Strasbourg Europe (ICANS)
Strasbourg, Grand Est, 67200
- Completed
IUCT-Oncopole
Toulouse, Haure-Garrone, 31100
Italy10 sites
- Active, not recruiting
ASST degli Spedali Civili di Brescia
Brescia
- Completed
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
Milan, 20122
- Active, not recruiting
IRCCS Ospedale San Raffaele
Milan, 20132
- Completed
ASST di Monza-Ospedale San Gerardo
Monza
- Completed
Fondazione Monza e Brianza per il Bambino e la sua Mamma
Monza
- Completed
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
- Completed
Fondazione IRCCS Policlinico San Matteo
Pavia
- Active, not recruiting
Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Roma, 168
- Completed
AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita
Torino
- Completed
Citta della Salute e della Scienza di Torino - Ospedale le Molinette
Torino
Germany6 sites
- Completed
Universitaetsklinikum Carl Gustav Carus Dresden
Dresden, 01307
- Completed
Universitaetsklinikum Jena
Jena, 07740
- Completed
Universitaetsklinikum Leipzig
Leipzig, 04103
- Completed
Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
Mainz, 55131
- Active, not recruiting
Universitaetsklinikum Muenster
Münster, 48149
- Active, not recruiting
Universitatsklinikum Regensburg
Regensburg, 93053
United Kingdom6 sites
- Completed
Bristol Royal Hospital for Children
Bristol, BS2 8BJ
- Active, not recruiting
University Hospital of Wales
Cardiff
- Completed
Queen Elizabeth University Hospital
Glasgow
- Active, not recruiting
Hammersmith Hospital
London
- Active, not recruiting
King's College Hospital NHS Foundation Trust
London
- Completed
Royal Marsden Foundation Trust
London
Canada4 sites
- Active, not recruiting
McGill University Health Center - Research Institute
Montreal, Quebec, H3G 1A4
- Active, not recruiting
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
- Completed
Princess Margaret Hospital
Toronto, Ontario
- Active, not recruiting
Vancouver Coastal Health Authority
Vancouver, British Columbia, V5Z 1M9
Israel4 sites
- Active, not recruiting
Rambam Health Care Campus
Haifa, 3109601
- Active, not recruiting
Hadassah Medical Center Ein Karem
Jerusalem, 9112001
- Active, not recruiting
Chaim Sheba Medical Center
Ramat Gan, 5262160
- Active, not recruiting
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
South Korea4 sites
- Active, not recruiting
Pusan National University Hospital
Busan
- Completed
Korea University Anam Hospital
Seoul
- Active, not recruiting
Seoul National University Hospital
Seoul
- Completed
Severance Hospital
Seoul
Greece3 sites
- Active, not recruiting
University Hospital of West Attica - Attikon - Hematology Division
Athens
- Active, not recruiting
General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit
Eksochi, Thessaloniki, 57010
- Completed
University General Hospital of Patras
Pátrai, 26500
Singapore3 sites
- Active, not recruiting
National University Hospital
Singapore, 119074
- Completed
KK Women's and Children hospital
Singapore, 229899
- Completed
Singapore General Hospital
Singapore
Taiwan3 sites
- Completed
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 80756
- Active, not recruiting
China Medical University Hospital
Taichung, 40447
- Active, not recruiting
National Taiwan University Hospital
Taipei, 100
Australia2 sites
- Completed
The Royal Children's Hospital
Parkville, Victoria, 3052
- Completed
Westmead Hospital
Westmead
Belgium2 sites
- Active, not recruiting
Universitaire Ziekenhuizen Leuven
Leuven
- Active, not recruiting
AZ Delta
Roeselare
Portugal2 sites
- Completed
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)
Lisbon, 1099-023
- Completed
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
Porto
Poland1 site
- Completed
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
Gliwice, 44-102
About this study
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
This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.
Read the detailed description
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.
- Conditions
- Chronic Graft-versus-host-disease
- Being tested
- Axatilimab
- Keywords
- cGVHD, AGAVE-201, GVHD, graft versus host disease, graft-versus-host-disease
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxatilimabDrug
Also called Niktimvo, SNDX-6352
Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.
| Study group | Role | What they receive |
|---|---|---|
| Axatilimab Dose Cohort 1 | Experimental | Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years. Receives: Drug: Axatilimab |
| Axatilimab Dose Cohort 2 | Experimental | Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years. Receives: Drug: Axatilimab |
| Axatilimab Dose Cohort 3 | Experimental | Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years. Receives: Drug: Axatilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
The ORR was defined as the percentage of participants with objective response (complete response [CR] or partial response [PR]). CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site.
Measured: First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks)
Secondary outcomes (17)
ORR on Study as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD
Measured: Up to 2 years
Number of Participants With a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale
Measured: Up to 2 years
Duration of Response
Duration of response is defined as the time from initial partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.
Measured: Up to 2 years
Sustained Response Rate
Sustained response rate is defined as the number of participants with objective response lasting for at least 20 weeks (140 days) from the time of initial response. Responses will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD.
Measured: Up to 2 years
Organ-specific Response Rate
Organ-specific response is defined as the number of participants with objective response for the nine individual organs based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal [GI], lower GI, liver, lungs and joints and fascia).
Measured: Up to 2 years
Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD
Measured: Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid
Measured: Up to 2 years
Number of Participants Who Discontinue Corticosteroid Use
Measured: Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI)
Measured: Up to 2 years
Number of Participants Who Discontinue CNIs
Measured: Up to 2 years
Change From Baseline in Circulating Monocyte Number and Phenotype (CD14/16)
Measured: Baseline, up to 2 years
Number of Participants With Anti-Drug Antibody
Measured: Up to 2 years
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Measurable Concentration (AUC0-t)
Measured: Approximately 12 months
Number of Participants With Treatment-emergent Adverse Events
Measured: Up to 2 years
Change From Baseline in Bone Turnover Markers
Measured: Baseline, up to 2 years
Change From Baseline in Bone Density
Measured: Baseline, up to 2 years
Change From Baseline in Colony Stimulating Factor 1 (CSF-1) and Interleukin 34 (IL-34) Levels
Measured: Baseline, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2021
- Study start4 Mar 2021
- Primary completion7 Apr 2023
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-host-diseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 296 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ellen Hooper, M.D., Study director, Syndax Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04710576
- Sponsor's protocol ID
- SNDX-6352-0504
- Other IDs
- 2024-512978-99-00
- Acronym
- AGAVE-201
- Status last verified
- May 2026
- First submitted
- 5 Jan 2021
- Last updated
- 16 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang YO, Sokolov V, Volkova A, Liu X, Leon C, Kosinsky Y, Barker B, Zhang X, Ordentlich P, Sheng J, Chen X. Semimechanistic Population PK/PD Modeling of Axatilimab in Healthy Participants and Patients With Solid Tumors or Chronic Graft-Versus-Host Disease. Clin Pharmacol Ther. 2025 Mar;117(3):704-715. doi: 10.1002/cpt.3503. Epub 2024 Dec 20.
PubMed 39704205Wolff D, Cutler C, Lee SJ, Pusic I, Bittencourt H, White J, Hamadani M, Arai S, Salhotra A, Perez-Simon JA, Alousi A, Choe H, Kwon M, Bermudez A, Kim I, Socie G, Chhabra S, Radojcic V, O'Toole T, Tian C, Ordentlich P, DeFilipp Z, Kitko CL; AGAVE-201 Investigators. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024 Sep 19;391(11):1002-1014. doi: 10.1056/NEJMoa2401537.
PubMed 39292927