Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ibrutinib; Bortezomib; Dexamethasone
Intervention description: Ibrutinib 840 mg orally, once daily continuously starting day 1 of cycle 1 until confirmed disease progression, unacceptable toxicity or other protocol specified reason for discontinuation; Cycles 1-8: (21-day cycle): Bortezomib 1.3 mg/m^2 sub-cutaneously on days 1, 4, 8, and 11 of each Cycle Cycles 9-12: (42-day cycle): Bortezomib 1.3 mg/m^2 sub-cutaneously on days 1, 8, 22 and 29 of each Cycle; Cycles 1-8: (21-day cycle): Dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle Cycles 9-12: (42-day cycle): Dexamethasone 20 mg orally on days 1, 2, 8, 9, 22, 23, 29 and 30 of each cycle Cycles 13+ (28-day cycle): Dexamethasone 40 mg orally once weekly
Dose adjustment of dexamethasone to 10 mg on days specified during cycles 1-12 and 20 mg weekly during cycles 13+ is recommended for subjects >75 years of age.
Following implementation of Protocol Amendment 4, dexamethasone administration was reduced to Days 1, 4, 8 and 11 during each 21-day cycle (Cycles 1-8) and on Days 1, 8, 22, 29 on each 42-day cycle (Cycles 9-12) and unchanged thereafter.
Intervention MeSH terms: Dexamethasone; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bruton's Tyrosine Kinase; Bortezomib; Dexamethasone; Ibrutinib

Summary:

      This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in
      combination with bortezomib and dexamethasone for patients with relapsed or relapsed and
      refractory multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with multiple myeloma (MM) who have received 1-3 prior lines of therapy and
             have demonstrated disease progression since the completion of the most recent
             treatment regimen. (Subjects may have received prior bortezomib exposure if it does
             not meet the exclusion criteria for prior proteasome inhibitor use)

          -  Measurable disease defined by at least one of the following:

               -  Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A
                  (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM)
                  multiple myeloma SPEP ≥0.5 g/dL)

               -  Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis

          -  Adequate hematologic, hepatic and renal function

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

        Exclusion Criteria:

          -  Subject must not have primary refractory disease

          -  Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or
             carfilzomib)

          -  Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening

          -  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