A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease
Overview
- Phase
- Phase 1
- Intervention
- Ibrutinib
- Conditions
- Graft Versus Host Disease
- Sponsor
- Pharmacyclics LLC.
- Enrollment
- 45
- Locations
- 10
- Primary Endpoint
- Phase 2: Overall Response Rate as the Percentage of Participants With Response
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Steroid dependent or refractory classic chronic GVHD disease.
- •No more than 3 previous treatments for cGVHD.
- •Receiving baseline systemic glucocorticoid therapy (at stable dose) for cGVHD at study entry.
- •Men and women ≥18 years old.
- •Karnofsky performance status ≥60.
Exclusion Criteria
- •Known or suspected active acute GVHD.
- •Current treatment with sirolimus AND either cyclosporine or tacrolimus.
- •History of treatment with a tyrosine kinase inhibitor (eg, imatinib), purine analogs or other cancer chemotherapy in the 4 weeks prior to starting study drug.
- •Currently active, clinically significant cardiovascular disease.
- •Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines or a recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- •Progressive underlying malignant disease including post-transplant lymphoproliferative disease.
- •History of other malignancy (not including the underlying malignancy that was the indication for transplant)
- •Concomitant use of warfarin or other Vitamin K antagonists
- •Known bleeding disorders or hemophilia.
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
Arms & Interventions
Phase 1b: Dose Level 1
Subjects receive daily dose of 420 mg of Ibrutinib capsules
Intervention: Ibrutinib
Phase 1b: Dose Level 2
Subjects receive daily dose of 280 mg of Ibrutinib capsules
Intervention: Ibrutinib
Phase 1b: Dose Level 3
Subjects receive daily dose of 140 mg of Ibrutinib capsules
Intervention: Ibrutinib
Phase 2
Subjects receive daily dose of recommended phase 2 dose
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Phase 2: Overall Response Rate as the Percentage of Participants With Response
Time Frame: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Overall Response Rate is defined as the proportion of subjects who achieved complete response (CR) or partial response (PR). Response criteria are based on NIH cGVHD Response assessment (Pavletic 2006; Measurement of Therapeutic Response, ASBMT Web site).
Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.
Time Frame: 28 treatment days after last subject enrolled in Phase 1 dose level(s).
Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib
Secondary Outcomes
- To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Corticosteroid Requirement Changes Over Time(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD(From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months)
- Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Sustained Response Rate as the Percentage of Participants With Sustained Response(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)