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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04710576
Other study ID # SNDX-6352-0504
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date March 4, 2021
Est. completion date December 2024

Study information

Verified date June 2024
Source Syndax Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 241
Est. completion date December 2024
Est. primary completion date June 29, 2023
Accepts healthy volunteers No
Gender All
Age group 2 Years and older
Eligibility 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


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Australia The Royal Children's Hospital Parkville Victoria
Australia Westmead Hospital Westmead
Belgium Universitaire Ziekenhuizen Leuven Leuven
Belgium AZ Delta Roeselare
Canada CHU Sainte-Justine Montreal Quebec
Canada McGill University Health Center - Research Institute Montréal Quebec
Canada Princess Margaret Hospital Toronto Ontario
Canada Vancouver Coastal Health Authority Vancouver British Columbia
France CHU Amiens Picardie - Hopital Sud Amiens Hauts-de-France
France CHU de Grenoble La Tronche Auvergne-Rhône-Alpes
France CHRU de Lille - Hopital Claude Huriez Lille Hauts-de-France
France CHRU de Nancy - Hôpitaux de Brabois Nancy
France CHU de Nantes - Hôtel-Dieu Nantes
France Hopital Pitie Salpetriere Paris
France Hopital Saint Louis Paris
France CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie Pessac
France HCL Centre Hospitalier Lyon Sud Pierre-Bénite
France Institut de cancérologie Strasbourg Europe (ICANS) Strasbourg Grand Est
France IUCT-Oncopole Toulouse Haure-Garrone
Germany Universitaetsklinikum Carl Gustav Carus Dresden Dresden
Germany Universitaetsklinikum Jena Jena
Germany Universitaetsklinikum Leipzig Leipzig
Germany Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz Mainz
Germany Universitaetsklinikum Muenster Münster
Germany Universitatsklinikum Regensburg Regensburg
Greece University Hospital of West Attica - Attikon - Hematology Division Athens
Greece General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit Exochí Thessaloniki
Greece University General Hospital of Patras Patras
Israel Rambam Health Care Campus Haifa
Israel Hadassah Medical Center Ein Karem Jerusalem
Israel Chaim Sheba Medical Center Ramat Gan
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Italy ASST degli Spedali Civili di Brescia Brescia
Italy Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano Milano
Italy IRCCS Ospedale San Raffaele Milano
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
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Italy Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore Roma
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
Korea, Republic of Pusan National University Hospital Busan
Korea, Republic of Korea University Anam Hospital Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital Seoul
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii Gliwice
Portugal Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa) Lisboa
Portugal Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE Porto
Singapore KK Women's and Children hospital Singapore
Singapore National University Hospital Singapore
Singapore Singapore General Hospital Singapore
Spain Hospital Clinic Barcelona Barcelona
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Universitario Donostia Donostia
Spain Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves Granada
Spain Hospital General Universitario Gregorio Maranon Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Hospital Universitario Puerta de Hierro Majadahonda
Spain Hospital Clinico Universitario de Salamanca Salamanca
Spain Hospital Universitario Marquis de Valdecilla Santander
Spain Hospital Universitario Virgen del Rocio Sevilla Seville
Spain Hospital Clinico Universitario de Valencia Valencia
Spain Hospital Universitari i Politecnic La Fe Valencia
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung
Taiwan China Medical University Hospital Taichung
Taiwan National Taiwan University Hospital Taipei
United Kingdom Bristol Royal Hospital for Children Bristol
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 States University of Michigan Ann Arbor Michigan
United States Emory University Atlanta Georgia
United States Northside Hospital Atlanta Georgia
United States Johns Hopkins Kimmel Cancer Center Baltimore Maryland
United States University of Alabama at Birmingham Birmingham Alabama
United States University of Alabama at Birmingham - Children's of Alabama Birmingham Alabama
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States University of Virginia Medical Center Charlottesville Virginia
United States The University of Chicago Medical Center (UCMC) Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States The Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Henry Ford Hospital Detroit Michigan
United States City of Hope Duarte California
United States University of Florida (UF) Gainesville Florida
United States MD Anderson Cancer Center Houston Texas
United States Franciscan Health Indianapolis Indianapolis Indiana
United States Indiana University Health Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States Mayo Clinic - Jacksonville Jacksonville Florida
United States University of California, Los Angeles (UCLA) - Medical Center Los Angeles California
United States University of Southern California Norris Comprehensive Cancer Center Los Angeles California
United States The Cleveland Clinic Foundation Lyndhurst Ohio
United States University of Wisconsin - Carbone Cancer Center Madison Wisconsin
United States University of Miami Miami Florida
United States Froedtert Hospital and the Medical College of Wisconsin Milwaukee Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States Vanderbilt University Medical Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Tulane University Medical Center New Orleans Louisiana
United States Weill Medical College of Cornell University New York New York
United States University of Oklahoma - Health Sciences Center Oklahoma City Oklahoma
United States AdventHealth Orlando Orlando Florida
United States University of Pittsburgh Medical Center - Hillman Cancer Center Pittsburgh Pennsylvania
United States Oregon Health & Science University Portland Oregon
United States Mayo Clinic - Rochester Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States Intermountain Healthcare Salt Lake City Utah
United States University of Utah Salt Lake City Utah
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Stanford Cancer Center Stanford California
United States Stony Brook University Medical Center Stony Brook New York
United States Moffitt Tampa Florida
United States Children's National Medical Center Washington District of Columbia
United States Wake Forest Winston-Salem North Carolina
United States University of Massachusetts Memorial Medical Center Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Syndax Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Response Rate in the First 6 Cycles The overall response rate will be assessed by the number of participants with objective response by Cycle 7 (28-day cycles), Day 1, with responses defined by the 2014 NIH consensus criteria. Up to Day 169
Secondary Number of Participants with a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale Approximately 30 months
Secondary 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. Approximately 30 months
Secondary 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 by organ system will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD. Approximately 30 months
Secondary 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). Approximately 30 months
Secondary Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD Approximately 30 months
Secondary Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid Approximately 30 months
Secondary Number of Participants who Discontinue Corticosteroid Use Approximately 30 months
Secondary Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI) Approximately 30 months
Secondary Number of Participants who Discontinue CNIs Approximately 30 months
Secondary Change from Baseline in Circulating Monocyte Levels Baseline, approximately 30 months
Secondary Number of Participants with Anti-Drug Antibody Approximately 30 months
Secondary Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of Last Measurable Concentration (AUC0-t) Approximately 12 months
Secondary AUC from Time 0 to Infinity (AUC0-inf) Approximately 12 months
Secondary Observed Maximum Plasma Concentration (Cmax) Approximately 12 months
Secondary Time to Observed Maximum Plasma Concentration (Tmax) Approximately 12 months
Secondary Number of Participants with Treatment-emergent Adverse Events Approximately 30 months
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