Chronic graft-versus-host disease (cGVHD)
Conditions
Interventions
Experimental group:Axatilimab
Sponsors
Peking University People's Hospital
Eligibility
Sex/Gender
All
Age
12 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Be at least 12 years old at the time of signing the ICF. 2. Able to understand and be willing to sign the written ICF of this study. (1) For subjects aged 12 to 17 years, parents/guardians must provide informed consent for child subjects; If applicable, child subjects should also sign a child consent form. 3. Patients with refractory or relapsed Chinese cGVHD after allo-HSCT, and subjects with active cGVHD requiring systemic immunosuppressive therapy after previous corticosteroids and at least 1 other appropriate anti-refractory or relapsed cGVHD treatment. (1) According to the 2014 NIH Consensus Development Project on the criteria for cGVHD clinical trials (Jagasia et al 2015), active cGVHD was defined as the presence of cGVHD symptoms and signs. (2) Refractory disease was defined as meeting any of the following criteria: 1) appearance of one or more new disease sites during cGVHD treatment. 2) progression of the existing disease site despite at least 1 month of standard cGVHD or investigational therapy. 3) subjects did not achieve remission from prior cGVHD therapy within 3 months and were deemed by the attending physician to require new systemic therapy. (3) According to the 2014 NIH consensus criteria, doctors considered that new systemic therapy was needed by specific organ evaluation or global evaluation criteria (Lee et al 2015). Recurrent cGVHD was defined as symptomatic active disease after initial remission of previous treatment. 4. Subjects may have persistent manifestations of active aGVHD and cGVHD (overlap syndrome), as defined by the 2014 NIH Consensus Development Project on criteria for cGVHD clinical trials. 5. Karnofsky performance status Scale score >=60 (if age >=16 years); Lansky performance-status score >=60 (if age =1.0×10^9/L (in the absence of growth factors within 1 week before enrollment). (2) platelet count >=50×10^9/L (without use of growth factors or blood transfusion within 2 weeks before enrollment). (3) ALT and AST=30 mL/min/1.73 m2 (calculated according to Cockcroft-Gault formula for adult subjects and Schwartz formula for children); 8. Concomitant systemic corticosteroids were allowed but not required. Topical and inhaled corticosteroids were allowed. If the subject was using corticosteroids, the dose had to be stable for at least 2 weeks before the start of the study treatment. 9. Concomitant use of CNI or mTOR inhibitors is permitted but not required (CNI/mTOR inhibitors may be initiated for prophylaxis or treatment of cGVHD, but the reason for initiating treatment must be recorded in the database). If the subject was using CNI or mTOR inhibitors, the following criteria had to be met: (1) The dose must have been stable for at least 2 weeks before the start of the study treatment. (2) The dose must be within the therapeutic dose range. 10. Willingness to avoid pregnancy or childbirth according to the following criteria. (1)Fertile male subjects must agree to use appropriate contraception from screening until 90 days after the last dose of study treatment (spermatogenic cycle) and must not donate sperm during this period. Subject
Exclusion criteria
Exclusion criteria: 1. Has aGVHD 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. Active symptomatic myositis. 5. History or other evidence of severe illness, uncontrolled infection, allergy to excipients (see formulation details in the IB), or any other conditions that would make the participant, in the opinion of the investigator, unsuitable for the study. 6. Positive HIV status. 7. History of latent or active TB, including either one of following: a. Signs or symptoms suggestive of active TB upon medical history and/or physical examination. b. Recent close contact with a person with active TB. 8. Positive QuantiFERON and/or T-spot TB test at screening. 9. Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg). Participants with negative HBsAg and positive total HBcAb and/or HBsAb should be excluded if quantitative HBV DNA test result is >= 20 IU/mL at the time of screening. Participants who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 10. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years before Cycle 1 Day 1 unless previously treated with curative intent (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) and approved by the sponsor's medical monitor. 11. Pregnant or breastfeeding. 12. Previous exposure to CSF-1R targeted therapies. 13. Use of any agent other than corticosteroids, CNIs, or mTOR inhibitors for the treatment of cGVHD within 2 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. 14. Has received an investigational treatment within 28 days prior to the start of study treatment. 15. Currently participating in any other interventional study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response;Frequency and severity of AEs; | — |
Secondary
| Measure | Time frame |
|---|---|
| Frequency and severity of AEs;Corticosteroid discontinuation;serum biomarker profile;Organ-specific response;dose (or equivalent) of calcineurin inhibitors;Discontinuation of calcineurin inhibitor;Duration of response, DOR;PK;Dose (or equivalent) of corticosteroids;Immunogenicity;Objective response;mLSS score; | — |
Countries
China
Contacts
Public ContactXiaohui Zhang
Peking University People's Hospital
Outcome results
None listed