Ibrutinib and Rituxan for Chronic GVHD

Phase II Trial Evaluating the Safety and Efficacy of Combined CD20- and BTK-Targeted B Cell Depleting Therapy With Rituximab and Ibrutinib in the Primary Treatment of Chronic Graft-Versus-Host Disease

This is a phase II trial evaluating the safety and efficacy of the combination of Ibrutinib and Rituximab as primary treatment of chronic GVHD. We plan to enroll 35 patients on this study. Patients will be formally monitored monthly for 12 months to evaluate for outcome and safety endpoints. All other assessments will be done at the physician's discretion or institutional standards. All patients, responders and treatment failures, will be followed for a period of one year from the time of initiation of therapy. The primary endpoint will be the proportion of patients that are alive and off all systemic IST at 12 months following initiation of treatment.

Inclusion Criteria:

• First episode of systemic immunosuppression-requiring cGVHD, defined as classic or overlap cGVHD by the NIH consensus criteria.
• Previously untreated cGVHD, defined by having received <10 days of corticosteroids or alternative systemic immunosuppressive agent started specifically for a new diagnosis of cGVHD.
• KPS 70% or greater

Exclusion Criteria:

• Late persistent or recurrent acute GVHD
• Active uncontrolled infection
• History of HIV infection; active HBV or HCV infection
• Inability to tolerate oral medications
• Progressive or recurrent malignancy following allogeneic transplant
• Exposure to BTK inhibitor following transplant
• Received prior treatment with ECP for cGVHD