Back to Trials
NCT04710576PHASE2Recruiting

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

Syndax Pharmaceuticals

Start Date

3/4/2021

Completion Date

9/1/2027

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.

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.

Eligibility Criteria

Age Range: 2 years to No maximum

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).

Interventions

DRUG

Axatilimab

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Chronic Graft-versus-host-disease

Locations

University of Alabama at Birmingham - Children's of Alabama

Birmingham, Alabama 35233

United States

University of Alabama at Birmingham

Birmingham, Alabama 35294

United States

City of Hope

Duarte, California 91010

United States

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

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

Los Angeles, California 90059

United States

Stanford Cancer Center

Stanford, California 94305

United States

Children's National Medical Center

Washington D.C., District of Columbia 20010

United States

University of Florida (UF)

Gainesville, Florida 32610

United States

Mayo Clinic - Jacksonville

Jacksonville, Florida 32224

United States

University of Miami

Miami, Florida 33136

United States

AdventHealth Orlando

Orlando, Florida 32806

United States

Moffitt

Tampa, Florida 33612

United States

Emory University

Atlanta, Georgia 30322

United States

Northside Hospital

Atlanta, Georgia 30342

United States

The University of Chicago Medical Center (UCMC)

Chicago, Illinois 60637

United States

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana 46202

United States

Franciscan Health Indianapolis

Indianapolis, Indiana 46237

United States

Tulane University Medical Center

New Orleans, Louisiana 70112

United States

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland 21231-2410

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts 01655

United States

University of Michigan

Ann Arbor, Michigan 48084

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55905

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08903

United States

Weill Medical College of Cornell University

New York, New York 10022

United States

Stony Brook University Medical Center

Stony Brook, New York 11794

United States

Wake Forest

Winston-Salem, North Carolina 27157

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

The Cleveland Clinic Foundation

Lyndhurst, Ohio 44195

United States

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oregon Health & Science University

Portland, Oregon 97239

United States

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Intermountain Healthcare

Salt Lake City, Utah 84111

United States

University of Utah

Salt Lake City, Utah 84112

United States

University of Virginia Medical Center

Charlottesville, Virginia 22908

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109

United States

University of Wisconsin - Carbone Cancer Center

Madison, Wisconsin 53792

United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

The Royal Children's Hospital

Parkville, Victoria 3052

Australia

Westmead Hospital

Westmead,

Australia

Universitaire Ziekenhuizen Leuven

Leuven,

Belgium

AZ Delta

Roeselare,

Belgium

Vancouver Coastal Health Authority

Vancouver, British Columbia V5Z 1M9

Canada

Princess Margaret Hospital

Toronto, Ontario

Canada

McGill University Health Center - Research Institute

Montreal, Quebec H3G 1A4

Canada

CHU Sainte-Justine

Montreal, Quebec H3T 1C5

Canada

CHU de Grenoble

La Tronche, Auvergne-Rhône-Alpes 38700

France

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, Grand Est 67200

France

IUCT-Oncopole

Toulouse, Haure-Garrone 31100

France

CHU Amiens Picardie - Hopital Sud

Amiens, Hauts-de-France 80054

France

CHRU de Lille - Hopital Claude Huriez

Lille, Hauts-de-France 59037

France

CHRU de Nancy - Hôpitaux de Brabois

Nancy,

France

CHU de Nantes - Hôtel-Dieu

Nantes,

France

Hopital Saint Louis

Paris, 75010

France

Hopital Pitie Salpetriere

Paris, 75013

France

CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie

Pessac,

France

HCL Centre Hospitalier Lyon Sud

Pierre-Bénite,

France

Universitaetsklinikum Carl Gustav Carus Dresden

Dresden, 01307

Germany

Universitaetsklinikum Jena

Jena, 07740

Germany

Universitaetsklinikum Leipzig

Leipzig, 04103

Germany

Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz

Mainz, 55131

Germany

Universitaetsklinikum Muenster

Münster, 48149

Germany

Universitatsklinikum Regensburg

Regensburg, 93053

Germany

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

Eksochi, Thessaloniki 57010

Greece

University Hospital of West Attica - Attikon - Hematology Division

Athens,

Greece

University General Hospital of Patras

Pátrai, 26500

Greece

Rambam Health Care Campus

Haifa, 3109601

Israel

Hadassah Medical Center Ein Karem

Jerusalem, 9112001

Israel

Chaim Sheba Medical Center

Ramat Gan, 5262160

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

ASST degli Spedali Civili di Brescia

Brescia,

Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122

Italy

IRCCS Ospedale San Raffaele

Milan, 20132

Italy

ASST di Monza-Ospedale San Gerardo

Monza,

Italy

Fondazione Monza e Brianza per il Bambino e la sua Mamma

Monza,

Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100

Italy

Fondazione IRCCS Policlinico San Matteo

Pavia,

Italy

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

Roma, 168

Italy

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

Torino,

Italy

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

Torino,

Italy

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

Gliwice, 44-102

Poland

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

Lisbon, 1099-023

Portugal

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto,

Portugal

National University Hospital

Singapore, 119074

Singapore

KK Women's and Children hospital

Singapore, 229899

Singapore

Singapore General Hospital

Singapore,

Singapore

Pusan National University Hospital

Busan,

South Korea

Korea University Anam Hospital

Seoul,

South Korea

Seoul National University Hospital

Seoul,

South Korea

Severance Hospital

Seoul,

South Korea

Hospital Universitario Virgen del Rocio

Seville, Seville 41013

Spain

Hospital Universitario Vall d'Hebron

Barcelona, 08035

Spain

Hospital Clinic Barcelona

Barcelona, 8032

Spain

Hospital Universitario Donostia

Donostia / San Sebastian,

Spain

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

Granada, 18014

Spain

Hospital General Universitario Gregorio Maranon

Madrid, 28007

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Universitario Puerta de Hierro

Majadahonda,

Spain

Hospital Clinico Universitario de Salamanca

Salamanca, 37007

Spain

Hospital Universitario Marquis de Valdecilla

Santander,

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

Hospital Universitari i Politecnic La Fe

Valencia, 46026

Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756

Taiwan

China Medical University Hospital

Taichung, 40447

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

Bristol Royal Hospital for Children

Bristol, BS2 8BJ

United Kingdom

University Hospital of Wales

Cardiff,

United Kingdom

Queen Elizabeth University Hospital

Glasgow,

United Kingdom

Hammersmith Hospital

London,

United Kingdom

King's College Hospital NHS Foundation Trust

London,

United Kingdom

Royal Marsden Foundation Trust

London,

United Kingdom