Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease

Pharmacyclics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Graft Versus Host Disease

Treatments: Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02195869

PCYC-1129-CA

Details and patient eligibility

About

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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Concurrent use of a strong cytochrome P450(CYP) 3A inhibitor.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

45 participants in 4 patient groups

Phase 1b: Dose Level 1

Experimental group

Description:

Subjects receive daily dose of 420 mg of Ibrutinib capsules

Treatment:

Drug: Ibrutinib

Phase 1b: Dose Level 2

Experimental group

Description:

Subjects receive daily dose of 280 mg of Ibrutinib capsules

Treatment:

Drug: Ibrutinib

Phase 1b: Dose Level 3

Experimental group

Description:

Subjects receive daily dose of 140 mg of Ibrutinib capsules

Treatment:

Drug: Ibrutinib

Phase 2

Experimental group

Description:

Subjects receive daily dose of recommended phase 2 dose

Treatment:

Drug: Ibrutinib