A Study of Oprozomib, Pomalidomide, and Dexamethasone in Adults With Primary Refractory or Relapsed and Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Oprozomib; Pomalidomide; Dexamethasone
Intervention description: Extended release (ER) tablets administered orally; Capsules for oral administration; Tablets for oral administration
Intervention MeSH terms: Dexamethasone; Pomalidomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the Phase 1 part of the study is to determine the maximum tolerated dose and
      assess the safety, tolerability and activity of oprozomib in combination with pomalidomide
      and dexamethasone in adults with primary refractory or relapsed and refractory multiple
      myeloma.

      The purpose of the Phase 3 part of the study is to compare the efficacy for adults with
      primary refractory or relapsed and refractory multiple myeloma who are randomized to either
      oprozomib or placebo in combination with pomalidomide and dexamethasone.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Multiple myeloma that is primary refractory or relapsed and refractory after at least
             2 lines of standard for multiple myeloma including:

               1. ≥ 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone
                  or in combination)

               2. In the dose-expansion and Phase 3 portions of the study only: In addition to the
                  above, treatment with adequate alkylator therapy, defined as:

             i. High-dose melphalan or other alkylating agent as conditioning for autologous or
             allogeneic stem cell transplant (SCT), or ii. ≥ 6 cycles of induction therapy, or iii.
             Progressive disease after ≥ 2 cycles

          2. Disease progression on or within 60 days of completion of the last therapy

          3. Measurable disease as indicated by 1 or more of the following:

               1. Serum M-protein ≥ 500 mg/dL

               2. Urine M-protein ≥ 200 mg/24 h

               3. For patients without measurable serum or urine M protein, serum free light chain
                  (SFLC): Involved free light chain (FLC) concentration ≥ 10 mg/dL provided SFLC
                  ratio is abnormal

          4. Males and females ≥ 18 years old

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

        Key Exclusion Criteria:

          1. Systemic chemotherapy with approved or investigational anticancer therapeutics,
             intended to treat underlying malignancy, within 3 weeks before the first dose or 6
             weeks for antibody therapy

          2. Dexamethasone at cumulative doses greater than 160 mg or equivalent within 21 days
             prior to the first dose of study treatment is not allowed. Use of topical or inhaled
             steroids is acceptable.

          3. Radiation therapy within 3 weeks before first dose. Radioimmunotherapy within 8 weeks
             before first dose.

          4. Plasmapheresis is not permitted at any time during the Screening period or while the
             subject is receiving study treatment. If a subject has started Screening procedures
             requiring plasmapheresis, or is anticipated to require plasmapheresis during or after
             the Screen

          5. Autologous SCT within 8 weeks or allogeneic SCT within 16 weeks prior to initiation of
             study treatment. Patients with prior allogeneic SCT should not have evidence of
             moderate-to-severe graft-versus-host disease (as defined in Filipovich 2005).

          6. Known hypersensitivity to any immunomodulatory drugs (IMiDs), including Grade 4 rash

          7. Prior treatment of any duration with pomalidomide

          8. Known hypersensitivity or intolerance to dexamethasone

          9. Prior exposure to oprozomib

         10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic
             ischemia, conduction abnormalities uncontrolled by conventional intervention, or
             myocardial infarction within 6 months before first dose.