NCT07484113Not yet recruitingPhase 1
IL6-receptor Inhibitor in Combination With Belumosudil for the Treatment of Belumosudil-refractory Chronic Graft-versus-host Disease (cGVHD)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Stanford University
- Enrollment
- 10
- Primary Endpoint
- Incidence of treatment-emergent adverse events
Study Overview
Brief Summary
A single-center, Phase 1, open-label, investigator-initiated clinical trial evaluating the safety, tolerability, and preliminary efficacy of sarilumab (anti-IL-6R) monotherapy as a rescue in adult patients with belumosudil-refractory chronic graft-versus-host disease (cGVHD).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Supportive Care
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 ≥
- •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.
- •14. Ability to provide written informed consent (or consent from legally authorized representative).
- •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.
Arms & Interventions
Dose Level 1: Sarilumab 150 mg + Belumosudil
Experimental
Participants receive Belumosudil 200 mg orally once daily and sarilumab 150 mg subcutaneously every 2 weeks.
Intervention: Sarilumab (Drug)
Dose Level 2: Sarilumab 200 mg + Belumosudil
Experimental
Participants receive Belumosudil 200 mg orally once daily and sarilumab 200 mg subcutaneously every 2 weeks.
Intervention: Belumosudil (Drug)
Dose Level 2: Sarilumab 200 mg + Belumosudil
Experimental
Participants receive Belumosudil 200 mg orally once daily and sarilumab 200 mg subcutaneously every 2 weeks.
Intervention: Sarilumab (Drug)
Dose Level 1: Sarilumab 150 mg + Belumosudil
Experimental
Participants receive Belumosudil 200 mg orally once daily and sarilumab 150 mg subcutaneously every 2 weeks.
Intervention: Belumosudil (Drug)
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events
Time Frame: From first dose through 6 months after treatment initiation
To evaluate the safety and tolerability of sarilumab monotherapy for the treatment of cGVHD after inadequate response to Belumosudil.
Secondary Outcomes
- Maximum Plasma Concentration (Cmax) of Sarilumab(Baseline through 6 months)
- Time to Maximum Plasma Concentration (Tmax) of Sarilumab(Baseline through 6 months)
- Area Under the Plasma Concentration-Time Curve (AUC) of Sarilumab(Baseline through 6 months)
- Incidence of serious infections(From first dose through 6 months)
- Overall response rate(Up to 6 months)
Investigators
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