A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)

NCT ID: NCT04710576

Last Updated: 2025-09-03

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

241 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-04

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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

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Chronic Graft-versus-host-disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Axatilimab Dose Cohort 1

Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.

Group Type EXPERIMENTAL

Axatilimab

Intervention Type DRUG

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.

Axatilimab Dose Cohort 2

Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.

Group Type EXPERIMENTAL

Axatilimab

Intervention Type DRUG

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.

Axatilimab Dose Cohort 3

Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.

Group Type EXPERIMENTAL

Axatilimab

Intervention Type DRUG

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.

Interventions

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Axatilimab

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.

Intervention Type DRUG

Other Intervention Names

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Niktimvo SNDX-6352

Eligibility Criteria

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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).
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syndax Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vedran Radojcic, M.D.

Role: STUDY_DIRECTOR

Syndax Pharmaceuticals

Locations

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University of Alabama at Birmingham - Children's of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California, Los Angeles (UCLA) - Medical Center

Los Angeles, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida (UF)

Gainesville, Florida, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Moffitt

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northside Hospital

Atlanta, Georgia, United States

Site Status

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, United States

Site Status

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Franciscan Health Indianapolis

Indianapolis, Indiana, United States

Site Status

Tulane University Medical Center

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Weill Medical College of Cornell University

New York, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Wake Forest

Winston-Salem, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

The Cleveland Clinic Foundation

Lyndhurst, Ohio, United States

Site Status

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Intermountain Healthcare

Salt Lake City, Utah, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Medical Center

Charlottesville, Virginia, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

The Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Universitaire Ziekenhuizen Leuven

Leuven, , Belgium

Site Status

AZ Delta

Roeselare, , Belgium

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Vancouver Coastal Health Authority

Vancouver, British Columbia, Canada

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Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

McGill University Health Center - Research Institute

Montreal, Quebec, Canada

Site Status

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status

CHU de Grenoble

La Tronche, Auvergne-Rhône-Alpes, France

Site Status

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, Grand Est, France

Site Status

IUCT-Oncopole

Toulouse, Haure-Garrone, France

Site Status

CHU Amiens Picardie - Hopital Sud

Amiens, Hauts-de-France, France

Site Status

CHRU de Lille - Hopital Claude Huriez

Lille, Hauts-de-France, France

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CHRU de Nancy - Hôpitaux de Brabois

Nancy, , France

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CHU de Nantes - Hôtel-Dieu

Nantes, , France

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Hopital Saint Louis

Paris, , France

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Hopital Pitie Salpetriere

Paris, , France

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CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie

Pessac, , France

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HCL Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

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Universitaetsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

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Universitaetsklinikum Jena

Jena, , Germany

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Universitaetsklinikum Leipzig

Leipzig, , Germany

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Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz

Mainz, , Germany

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Universitaetsklinikum Muenster

Münster, , Germany

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Universitatsklinikum Regensburg

Regensburg, , Germany

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General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit

Eksochi, Thessaloniki, Greece

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University Hospital of West Attica - Attikon - Hematology Division

Athens, , Greece

Site Status

University General Hospital of Patras

Pátrai, , Greece

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Rambam Health Care Campus

Haifa, , Israel

Site Status

Hadassah Medical Center Ein Karem

Jerusalem, , Israel

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Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

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ASST degli Spedali Civili di Brescia

Brescia, , Italy

Site Status

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano

Milan, , Italy

Site Status

IRCCS Ospedale San Raffaele

Milan, , Italy

Site Status

ASST di Monza-Ospedale San Gerardo

Monza, , Italy

Site Status

Fondazione Monza e Brianza per il Bambino e la sua Mamma

Monza, , Italy

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Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

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Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, , Italy

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AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita

Torino, , Italy

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Citta della Salute e della Scienza di Torino - Ospedale le Molinette

Torino, , Italy

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Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii

Gliwice, , Poland

Site Status

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)

Lisbon, , Portugal

Site Status

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, , Portugal

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National University Hospital

Singapore, , Singapore

Site Status

KK Women's and Children hospital

Singapore, , Singapore

Site Status

Singapore General Hospital

Singapore, , Singapore

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Pusan National University Hospital

Busan, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Severance Hospital

Seoul, , South Korea

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Hospital Universitario Virgen del Rocio

Seville, Seville, Spain

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Hospital Universitario Vall d'Hebron

Barcelona, , Spain

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Hospital Clinic Barcelona

Barcelona, , Spain

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Hospital Universitario Donostia

Donostia / San Sebastian, , Spain

Site Status

Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves

Granada, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

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Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Site Status

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Marquis de Valdecilla

Santander, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

Royal Marsden Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Greece Israel Italy Poland Portugal Singapore South Korea Spain Taiwan United Kingdom

References

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Wolff 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.

Reference Type DERIVED
PMID: 39292927 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2024-512978-99-00

Identifier Type: CTIS

Identifier Source: secondary_id

SNDX-6352-0504

Identifier Type: -

Identifier Source: org_study_id

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