Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet
Condition: Relapsed or Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Carfilzomib; Dexamethasone; Pomalidomide
Intervention description: Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study.; Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward.; Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.
Intervention MeSH terms: Dexamethasone; Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; RRMM; Open-label; First Relapse Multiple Myeloma; Second Relapse Multiple Myeloma; Refractory to Lenalidomide; Triplicate Treatment Regimen; Dexamethasone; Carfilzomib; Pomalidomide

Summary:

      A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with
      Pomalidomide and Dexamethasone
    

Eligibility criteria:

        Inclusion Criteria

          -  Subject has provided informed consent prior to initiation of any study specific
             activities or procedures.

          -  Male or female subjects age ≥ 18 years

          -  First or second relapse of multiple myeloma by IMWG criteria (subjects refractory to
             the most recent line of therapy, excluding carfilzomib, are eligible)

          -  Refractory to lenalidamide

          -  Measurable disease with at least 1 of the following assessed within 28 days prior to
             enrollment:

               -  IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL

               -  IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL

               -  urine M-protein ≥ 200 mg per 24 hours

               -  in subjects without measurable serum or urine M-protein, serum-free light chain
                  (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio

          -  Must have at least a PR to at least 1 line of prior therapy

          -  Prior therapy with proteasome inhibitors is allowed. Subjects receiving prior
             carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity,
             did not relapse within 60 days from discontinuation of carfilzomib, and must have at
             least a 6 month carfilzomib treatment-free interval from their last dose of
             carfilzomib

          -  ECOG PS of 0 to 2

        Exclusion Criteria

          -  Primary refractory multiple myeloma

          -  Waldenström macroglobulinemia

          -  Multiple myeloma of IgM subtype

          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          -  Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by
             differential). If automated differential shows ≥ 20% of other cells, obtain manual
             differential to identify other cells.

          -  Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of
             amyloid plaques found on biopsy would be eligible if all other criteria are met)

          -  Previous diagnosis of amyloidosis associated with myeloma

          -  Myelodysplastic syndrome

          -  Toxicity requiring discontinuation of lenalidomide therapy

          -  Prior treatment with pomalidomide