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
Brief SummaryAGAVE-201 is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in patients with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy due to progression of disease, intolerability or toxicity.
Detailed DescriptionAGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in patients with recurrent or refractory active cGVHD who have received at least 2 prior lines of systemic therapy due to progression of disease, intolerability or toxicity. Disease progression is defined 1) by the NIH 2014 consensus criteria, either in terms of organ specific algorithm or global assessment or 2) as active, symptomatic cGVHD for whom the physician believes that a new line of systemic therapy is required.
Inclusion and Exclusion Criteria
- Patient must be 2 years of age or older, at the time of signing the informed consent.
- Patients who are allogeneic 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 (Jagasia 2015).
- Patients 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. - Patients 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.
- Patients 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 mL/min/1.73 m2 based on the Cockcroft-Gault formula in adult patients and Schwartz formula in pediatric patients.
- 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 patient 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 sirolimus 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 in this protocol. A parent/guardian should provide consent for pediatric patients unable to provide consent themselves; in addition, where applicable pediatric patients should sign their own assent form.
- Patients 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 patient, in the opinion of the Investigator, unsuitable for the study.
- Patients 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 (eg, 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 patient who is pregnant or breastfeeding.
- Previous exposure to CSF1-R targeted therapies.
- Taking agents for treatment of cGVHD other than corticosteroids and either a CNI or sirolimus is prohibited. See Inclusion Criteria 9 for guidelines regarding the appropriate use of corticosteroids, CNI, and sirolimus in combination with study treatment.
- For approved or commonly used agents, other than corticosteroids, CNI and sirolimus, 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.
- Patients should not be participating in any other interventional study. Pediatric patients are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.