Clinical Trials

Inclusion 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 as follows:

  • Absolute neutrophil count ≥ 1.0 × 10^9/L without growth factors within 1 week of study entry);

  • Platelet count ≥ 50 × 10^9/L (without transfusion within 2 weeks of study entry);

  • ALT, and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 × ULN;

  • For patients with suspected or documented liver cGVHD, ALT and AST ≤ 5 x ULN and total bilirubin ≤ 1.5 × ULN.

• Creatinine clearance (CrCl) ≥ 30 mL/min/1.73 m^2 based on the Cockcroft-Gault formula in adult patients and Schwartz formula in pediatric patients.

• Male and/or female participants. 

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Adolescent and adult male patients capable of fathering a child who are non-sterilized and who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the study intervention treatment period and 90 days after the last dose of study intervention. However, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period.

• Female patients, post-menarche, must provide evidence of either post-menopausal status or negative urinary or serum pregnancy test. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  • Menarche, regardless of age, is defined as having had the first occurrence of menstruation;

  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy);

  • Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy);

  • Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the study intervention treatment period and 90 days after the last dose of study intervention. Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female patients should also refrain from breastfeeding throughout this period.

• 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, the following criteria must be met:

  • 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. The CNI or sirolimus may have been started either for prophylaxis or for treatment of cGVHD the reason for initiating treatment must be recorded in the database). If a patient is taking either a CNI or sirolimus at study randomization, the following criteria must be met:

  • Be on a stable dose of CNI or sirolimus for at least 2 weeks prior to randomization;

  • The dose of the CNI or sirolimus must be within the therapeutic range.

• 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.

Exclusion Criteria:

• 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 above 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 an 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).

Eligibility last updated 11/1/21. Questions regarding updates should be directed to the study team contact.