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

Official title

IL6-receptor Inhibitor in Combination With Belumosudil for the Treatment of Belumosudil-refractory Chronic Graft-versus-host Disease (cGVHD)

Overview

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).

Interventions

• Drug Belumosudil
  Belumosudil (2-(3-(4-(1H-indazol-5-ylamino) quinazolin-2-yl) phenoxy)-N-isopropylacetamide-methane sulfonic acid salt), formerly also known as KD025, is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. Belumosudil will be provided as 200 mg tablets.
• Drug Sarilumab
  Sarilumab is an interleukin-6 (IL-6) receptor antagonist FDA approved for treatment of: * Adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). * Adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. Sarilumab will be provided as single-use 1.14 ml prefilled glass syr

Primary outcome measures

• Incidence of treatment-emergent adverse events [Time frame: From first dose through 6 months after treatment initiation]

Secondary outcome measures (5)

• Maximum Plasma Concentration (Cmax) of Sarilumab [Time frame: Baseline through 6 months]
• Time to Maximum Plasma Concentration (Tmax) of Sarilumab [Time frame: Baseline through 6 months]
• Area Under the Plasma Concentration-Time Curve (AUC) of Sarilumab [Time frame: Baseline through 6 months]
• Incidence of serious infections [Time frame: From first dose through 6 months]
• Overall response rate [Time frame: Up to 6 months]

Eligibility criteria

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.

14\. 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Supportive care

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07484113 · IRB-83208 · NCI-2026-03510

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗