Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma

A Randomized Multicenter Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma

Phase 1 is an open-label, dose finding, multicenter study of ibrutinib in combination with pomalidomide and dexamethasone in subjects with relapsed/refractory multiple myeloma.

Phase 2b is a randomized, double-blind, multicenter study of ibrutinib or placebo, in combination with pomalidomide and dexamethasone in subjects with relapsed/refractory multiple myeloma.

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine, and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with pomalidomide and dexamethasone in subjects with relapsed/refractory multiple myeloma.

Inclusion Criteria:

• Subjects with relapsed/refractory MM who have received at least two prior lines of therapy including lenalidomide and either bortezomib or carfilzomib and have demonstrated disease progression on or within 60 days of the completion of the most recent treatment regimen.

• Measurable disease defined by at least ONE of the following:

  1. Serum monoclonal protein (SPEP) ≥1 g/dL.
  2. Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine.

• Adequate hematologic, hepatic, and renal function

• ECOG performance status of ≤ 2

Exclusion Criteria:

• Subject must not have primary refractory disease
• Plasma cell leukemia, primary amyloidosis or POEMS syndrome
• Unable to swallow capsules or disease significantly affecting gastrointestinal function
• Requires treatment with strong CYP3A inhibitors
• Women who are pregnant or breast feeding.