IL6-receptor Inhibitor Iwith Belumosudil for the Treatment of Belumosudil-refractory cGVHD

Inclusion criteria

• Age ≥ 18 years
• Active cGVHD and currently receiving belumosudil 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).
• Persistent cGVHD manifestations and systemic therapy indicated.
• Karnofsky Performance Score of ≥ 60.

Laboratory Parameters:

• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 50 x 109/L
• ALT and AST < 1.5 × ULN
• Total bilirubin ≤ 1.5 × ULN
• Glomerular filtration rate (GFR) ≥ 30 ml/min/1.73m2

General Criteria:

• 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 provide written informed consent (or consent from legally authorized representative). 15. Minimum weight of 63 kg

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.

General Criteria:

• Pregnant or breastfeeding.
• History or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the sponsor-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 PSA over 12 months
• QTc(F) > 480 ms
• Sponsor-investigator deems subject unlikely to adhere to study procedures/treatment.
• Investigational agent, device, or procedure within 28 days of first dose (or 5 half-lives, whichever longer).
• Active TB or a history of incompletely treated TB regardless of screening Quantiferon Result.