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.
Study 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.
Eligibility
Sex
ALL
Min age
2 Years
Max age
—
Healthy volunteers
No
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).
Primary outcome measure(s)
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) 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.
Trial sites (121)
Facility
City
Region
Status
University of Alabama at Birmingham - Children's of Alabama
Birmingham
Alabama
Completed
University of Alabama at Birmingham
Birmingham
Alabama
Recruiting
City of Hope
Duarte
California
Active Not Recruiting
University of Southern California Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
University of California, Los Angeles (UCLA) - Medical Center
Los Angeles
California
Completed
Stanford Cancer Center
Stanford
California
Active Not Recruiting
Children's National Medical Center
Washington D.C.
District of Columbia
Active Not Recruiting
University of Florida (UF)
Gainesville
Florida
Completed
Mayo Clinic - Jacksonville
Jacksonville
Florida
Active Not Recruiting
University of Miami
Miami
Florida
Recruiting
AdventHealth Orlando
Orlando
Florida
Completed
Moffitt
Tampa
Florida
Active Not Recruiting
Emory University
Atlanta
Georgia
Recruiting
Northside Hospital
Atlanta
Georgia
Active Not Recruiting
The University of Chicago Medical Center (UCMC)
Chicago
Illinois
Recruiting
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis
Indiana
Active Not Recruiting
Franciscan Health Indianapolis
Indianapolis
Indiana
Completed
Tulane University Medical Center
New Orleans
Louisiana
Completed
Johns Hopkins Kimmel Cancer Center
Baltimore
Maryland
Completed
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Active Not Recruiting
University of Massachusetts Memorial Medical Center
Worcester
Massachusetts
Active Not Recruiting
University of Michigan
Ann Arbor
Michigan
Active Not Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
Recruiting
Henry Ford Hospital
Detroit
Michigan
Completed
University of Minnesota
Minneapolis
Minnesota
Completed
Mayo Clinic - Rochester
Rochester
Minnesota
Active Not Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Active Not Recruiting
Weill Medical College of Cornell University
New York
New York
Active Not Recruiting
Stony Brook University Medical Center
Stony Brook
New York
Active Not Recruiting
Wake Forest
Winston-Salem
North Carolina
Completed
Cincinnati Children's Hospital Medical Center
Cincinnati
Ohio
Completed
University Hospitals Cleveland Medical Center
Cleveland
Ohio
Completed
The Ohio State University Comprehensive Cancer Center
Columbus
Ohio
Recruiting
The Cleveland Clinic Foundation
Lyndhurst
Ohio
Active Not Recruiting
University of Oklahoma - Health Sciences Center
Oklahoma City
Oklahoma
Active Not Recruiting
Oregon Health & Science University
Portland
Oregon
Recruiting
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh
Pennsylvania
Recruiting
Vanderbilt University Medical Center
Nashville
Tennessee
Active Not Recruiting
+ 81 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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