Randomized, Double-Blind Phase 3 Study of Ibrutinib versus Placebo in Combination with Corticosteroids in Patients with New-Onset cGVHD

Chronic graft-versus-host disease (cGVHD) is a common complication of allogeneic stem-cell transplantation. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton’s tyrosine kinase indicated for the treatment of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, recently received FDA breakthrough therapy and orphan drug designation for the treatment of patients with cGVHD who did not respond to ≥1 lines of systemic therapy. This designation was based, in part, on prior data presented by Miklos and colleagues, in which ibrutinib was shown to achieve an overall response rate of 67% in patients with steroid relapsed/refractory cGVHD (Miklos. Blood. 2016).

In this phase 3, randomized, controlled, double-blind study, investigators seek to evaluate the 24-week response rate of ibrutinib versus placebo in combination with prednisone. Patients with newly diagnosed moderate or severe cGVHD will be randomized to receive either oral ibrutinib or placebo in combination with oral prednisone. Ibrutinib or placebo will be given until unacceptable toxicity, relapse of underlying disease, death, or the need for a new systemic treatment for progressive cGVHD. To be eligible for the study, patients must be aged ≥12 years, must require systemic treatment with corticosteroids, and must have no prior systemic treatment for cGVHD.

The study’s primary end point is response rate (complete or partial response) at 24 weeks. To count toward the numerator, response must occur in the absence of both new therapy for cGVHD and relapse/return of the underlying disease that was the indication for transplant. Secondary end points include corticosteroid dose reduction, withdrawal of all immunosuppressants at 48 weeks, overall survival, response rate at 48 weeks, and safety. Recruitment is planned for approximately 186 patients.

Miklos DB, et al. ASCO Abstract TPS7072.