Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: PCI-32765; Dexamethasone
Intervention MeSH terms: Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PCI-32765; Multiple Myeloma; Relapsed Refractory Multiple Myeloma; Bruton's Tyrosine Kinase

Summary:

      The primary objective of this study is to determine the efficacy of PCI-32765, both as a
      single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and
      refractory Multiple Myeloma (MM)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of symptomatic MM with measurable disease, defined here as having at least
             one of the following:

               1. Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein
                  electrophoresis (SPEP)

               2. Urine M-protein ≥200 mg/24 hrs

               3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L)
                  provided serum FLC ratio is abnormal

          -  Relapsed or relapsed and refractory MM after receiving at least 2 but no more than 5
             previous lines of therapy, 1 of which must be an immunomodulator.

          -  Refractory myeloma (to most recent treatment) is defined as disease that is
             nonresponsive while on treatment or progressive disease within 60 days after the
             completion of preceding treatment. Nonresponsive disease is defined as either failure
             to achieve minimal response or development of progressive disease while on therapy.

          -  Men and women ≥18 years of age.

          -  ECOG performance status of ≤ 1.

        Exclusion Criteria:

          -  Subject must not have primary refractory disease defined as disease that is
             nonresponsive in subjects who have never achieved a minor response (MR) or better with
             any therapy.

          -  Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS)
             syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.

          -  Plasma cell leukemia.

          -  Primary amyloidosis.

          -  Certain exclusions on prior therapy.

          -  ANC <0.75 x 10^9/L independent of growth factor support.

          -  Platelets <50 x 10^9/L) independent of transfusion support.

          -  AST or ALT ≥3.0 x upper limit of normal (ULN).

          -  Total bilirubin >2.5 x ULN, unless due to Gilbert's syndrome.

          -  Creatinine >2.5 mg/dL.

          -  Unable to swallow capsules or disease significantly affecting gastrointestinal
             function.

          -  Requires anti-coagulation with warfarin or a vitamin K antagonist. Requires treatment
             with strong CYP3A4/5 inhibitors.