A Study of Ibrutinib in Combination With Corticosteroids versus Placebo in Combination With Corticosteroids in Patients with New Onset Chronic Graft Versus Host Disease (cGVHD)

INTERVENTION: Product Name: Ibrutinib Product Code: PCI‐32765 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Ibrutinib CAS Number: 936563‐96‐1 Current Sponsor code: PCI‐32765 Other descriptive name: IBRUTINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 140‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Chronic Graft Versus Host Disease (cGVHD) ; MedDRA version: 19.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 ‐ Immune system disorders Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of ibrutinib in combination with prednisone (Arm A) versus placebo in combination with prednisone (Arm B) based on the response rate at 24 weeks as determined by NIH Consensus Development Project criteria in subjects with new onset moderate to severe cGVHD. Primary end point(s): The primary endpoint is the response rate at 24 weeks. Response will be defined by the NIH Consensus Development Project Criteria (2014) and must occur:; ‐ In the absence of new therapy for cGVHD; In the absence of relapse or return of the underlying disease that was the indication for transplant (or post transplant; lymphoproliferative disease [PTLD]), or death Secondary Objective: To compare the two treatment arms in terms of the following:; Efficacy; ‐ Proportion of subjects obtaining steroid dose level less than 0.15 mg/kg/d at 24 weeks; ‐ Withdrawal of all immunosuppressants (with the exception of ibrutinib/placebo) at 48 weeks; ‐ Overall survival (OS); ‐ Response rate at 48 weeks; Safety; ‐ Safety and tolerability; ‐ Differences in steroid‐related morbidities (eg, hyperglycemia, hypertension) Timepoint(s) of evaluation of this end point: 24 weeks SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints will assess for additional clinical benefits including corticosteroid dose reduction, withdrawal of all immunosuppressants, and overall survival (OS). Timepoint(s) of evaluation of this end point: Timepoints for the secondary end points are detailed in the 'Schedule of assessments' in Appendix A of the protocol INCLUSION CRITERIA: Prior to randomization, each potential subject must satisfy all of the following inclusion criteria. Disease related 1. New onset moderate or severe cGVHD as defined by the NIH Consensus Development Project Criteria (2014). 2. History of an allogeneic hematopoietic cell transplant. 3. Need for systemic treatment with corticosteroids for cGVHD. 4. No previous systemic treatment for cGVHD (including extracorporeal photopheresis [ECP]). 5. Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but the doses of these medications must have been stable for at least 2 weeks prior to Screening. Prednisone dose must also be at or below 0.5 mg/kg/d at the time of randomization unless started within the previous 7 days for cGVHD. 6. Participants may have received pre‐transplant ibrutinib for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma, but must not have received a BTK