Sarilumab with Belumosudil for the Treatment of Belumosudil-Refractory Chronic Graft-versus-Host Disease

Inclusion Criteria

• Active cGVHD currently receiving belumosudil after at least 2 prior systemic therapies with inadequate response (defined as disease progression at any time or failure to achieve at least a partial response after a minimum of 3 months of belumosudil therapy, and for whom the treating physician believes a new systemic therapy is required)
• Age ≥ 18 years
• Persistent cGVHD manifestations and systemic therapy
• Karnofsky Performance Score of ≥ 60
• Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky performance status
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 50 x 10^9/L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 × ULN
• Minimum weight of 63 kg
• Negative urine pregnancy test at screening for females of childbearing potential
• Sexually active females of childbearing potential must agree to use two accepted methods of contraception during treatment and for 3 months after their last dose
• Sexually active male subjects with female partners of childbearing potential must agree to use two accepted methods of contraception and refrain from sperm donation during treatment and for at least 3 months after their last dose
• Ability to understand and the willingness to provide written informed consent (or consent from legally authorized representative)

Exclusion Criteria

• Not on a stable systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus are allowed. Systemic investigational GVHD treatments are not permitted)
• Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening
• Current treatment with ibrutinib or ruxolitinib. Prior treatment is allowed with a washout of at least 1 week prior to randomization
• Pregnant or breastfeeding
• History or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease)
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) or history of human immunodeficiency virus (HIV)
• Malignancy diagnosed within 3 years (other than malignancy for which transplant was performed), with the exception of: * Completely resected basal cell or squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Resected breast ductal carcinoma in situ * Prostate cancer with Gleason score < 6 and stable prostate specific antigen (PSA) over 12 months
• Fridericia's corrected QT interval (QTc[F]) > 480 ms
• Investigator deems subject unlikely to adhere to study procedures/treatment
• Investigational agent, device, or procedure within 28 days of first sarilumab dose (or 5 half-lives, whichever longer)
• Active tuberculosis (TB) or a history of incompletely treated TB regardless of screening Quantiferon result