Study of Bendamustine and IXAZOMIB (MLN9708) Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma

INCLUSION CRITERIA

• Male or female patients 18 years or older.
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patients who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice two effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
• Patients must have have histologically or cytologically confirmed symptomatic Multiple Myeloma, who are non-responsive to or ineligible for autologous stem cell transplant, and who progress after prior exposure to proteasome inhibitor (bortezomib, carfilzomib) and lenalidomide or pomalidomide or thalidomide (IMID); and refractory/progressing to at least one of these agents and must meet at least one of the following parameters of measurable disease:
• Measurable levels of monoclonal protein (M protein): > 1 g/dL of immunoglobin G (IgG) or immunoglobin M (IgM) M-protein or > 0.5 g/dL immunoglobin A (IgA) or immunoglobin D (IgD) M protein on serum protein electrophoresis OR > 200 mg/24h of free light chain proteinuria on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to registration OR > 10 mg/dL involved free light chain on serum free light chain testing with an abnormal kappa:lambda light chain ratio.
• Patients with lytic bone disease, defined as at least one lytic lesion that can be accurately measured in at least one dimension.
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• Patients are eligible after autologous or allogeneic stem cell transplantation. Allogeneic transplantation can be enrolled only if they have no ongoing transplant related side effects.
• Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1, 000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions or granulocyte-colony stimulating factor (G-CSF) can be used to help patients meet eligibility criteria but are not allowed within 3 days before study enrollment.
• Total bilirubin >< 1.5 x the ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN.
• Calculated creatinine clearance ≥ 30 mL/min.

EXCLUSION CRITERIA

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy except for peripheral neuropathy, which is addressed in exclusion criteria no. #14.
• Major surgery within 14 days before enrollment.

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