NCT03616184

Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids

A Single Arm, Open Label, Phase II Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: University of Nebraska · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of the study is to examine the efficacy of ruxolitinib in patients with sclerotic chronic graft-versus-host disease (GVHD).

Detailed description

Chronic graft-versus-host-disease (GVHD) is a major complication of allogeneic hematopoietic cell transplant that impairs quality of life, and is associated with significant morbidity and mortality. Management of chronic GVHD with prednisone is associated with an overall response rate of approximately 60%, and a complete response rate of approximately 30% but sclerotic features do not respond as well. Based on the biology of chronic GVHD and available preliminary evidence, the investigators hypothesize that ruxolitinib will be effective in the management of sclerotic chronic GVHD. The study is an open label, phase II multicenter trial designed to evaluate the efficacy of ruxolitinib as a salvage treatment for patients with sclerotic GVHD (sclerosis or fasciitis). The primary objective is to determine the proportion of patients with response rate (complete and partial responses) in skin and/or joint, as determined by 2014 NIH (National Institutes of Health) consensus criteria, at 6 months of therapy with ruxolitinib. Eligibility criteria includes adult patients with chronic GVHD and skin, joint and/or fascia sclerosis, who have received systemic corticosteroids for \>12 months and at least one additional line of therapy OR systemic corticosteroids and at least two additional lines of therapy for chronic GVHD. A sample size of 47 patients (43 evaluable patients and estimated 10% dropout) will allow an α of 0.044 and a power of 84% to test the null hypothesis response rate of 25% compared to an alternative of 45%. Subjects will receive ruxolitinib for 6 months for the treatment of sclerotic chronic GVHD. Subjects will be evaluated for GVHD status as well as non-relapse mortality, relapse of underlying malignancy and quality of life/functional status. Plasma cytokine levels and T/Natural Killer (NK) cell subset in peripheral blood will be measured at various time points. The response rate will be reported as a proportion and 95% exact confidence interval. If positive, the trial results will support other ongoing studies to establish the role of ruxolitinib in chronic GVHD in general and specifically in sclerotic chronic GVHD.

Conditions

• Graft-versus-host-disease (GVHD)

Interventions

Type	Name	Description
DRUG	Ruxolitinib	Patients with sclerotic chronic graft-versus-host disease (GVHD) will receive oral ruxolitinib at a dose of 10 mg twice daily. Doses may not exceed 10 mg twice daily. Ruxolitinib will be continued for 6 months. Patients who continue to have stable disease, mixed responses or partial/complete responses at the end of 6 months may continue the drug for a total of 12 months.

Timeline

• Start date: 2018-09-05
• Primary completion: 2022-01-22
• Completion: 2023-06-12
• First posted: 2018-08-06
• Last updated: 2023-10-05
• Results posted: 2023-08-14

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study