Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma

Exclusion Criteria

• •Subjects with any of the following will be excluded from participation in the study:
• •1. Peripheral neuropathy Grade ≥2.
• •2. Non-secretory multiple myeloma.
• •3. Any of the following laboratory abnormalities:
• •* ANC \<1,000/µL;
• •* Platelet count \<50,000/µL for subjects in whom \<50% of bone marrow nucleated cells are plasma cells; or a platelet count \<30,000/µL for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells;
• •* Creatinine clearance (CrCL) \<45 mL/min as measured directly or as calculated according to Cockcroft Gault formula;
• •* Corrected serum calcium \>13.5 mg/dL (\>3.4 mmol/L);
• •* Hemoglobin \<8 g/dL (\<4.9 mmol/L; prior red blood cell \[RBC\] transfusion or recombinant human erythropoietin use is permitted before study entry);
• •* Serum aspartate aminotransferase (AST) \>3.0 x upper limit of normal (ULN);
• •* Serum alanine aminotransferase (ALT) \>3.0 x ULN;
• •* Serum total bilirubin \>1.5 x ULN (\>3.0 x ULN for subjects with known Gilbert's disease).
• •4. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥5 years. Subjects may be entered earlier than 5 years if they have received curative treatment for the following:
• •* Basal cell carcinoma of the skin;
• •* Squamous cell carcinoma of the skin;
• •* Carcinoma in situ of the cervix;
• •* Carcinoma in situ of the breast;
• •Or if they have:
• •o Incidental histologic finding of prostate cancer (T1a or T1b using the TNM \[tumor, nodes, metastasis\] clinical staging system) or non metastatic prostate cancer that is in complete remission or does not require treatment.
• •5. Previous therapy with POM and/or MRZ.
• •6. History of allergic reaction or hypersensitivity to thalidomide, lenalidomide, bortezomib, carfilzomib, boron, mannitol, or DEX.
• •7. Grade ≥3 rash during prior thalidomide or lenalidomide therapy.
• •8. Gastrointestinal disease that may significantly alter the absorption of POM.
• •9. History of the following:
• •* Congestive heart failure of Class III or IV of the New York Heart Association (NYHA) classification;
• •* Myocardial infarction within 12 months prior to starting study treatment;
• •* Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
• •10. Any of the following within 14 days prior to initiation of study treatment:
• •* Plasmapheresis;
• •* Major surgery (kyphoplasty is not considered major surgery);
• •* Radiation therapy;
• •* Anti-myeloma drug therapy.
• •11. Received any investigational agents within 28 days or 5 half-lives (whichever is longer) prior to initiation of study treatment.
• •12. Conditions requiring chronic steroid or immunosuppressive treatment (eg, rheumatoid arthritis, multiple sclerosis, or lupus), which likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
• •13. Subjects may not receive corticosteroids (\>10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment (use of steroidal inhalation aerosol for asthma is permitted).
• •14. Unable or unwilling to undergo antithrombotic prophylactic treatment.
• •15. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, as determined by the Investigator.
• •16. Pregnant and/or breastfeeding females.
• •17. Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
• •18. Known seropositive for or active viral infection with hepatitis B virus (HBV), with the following exceptions:
• •* negative are eligible.
• •* Subjects who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible.
• •* Subjects who are seropositive because of hepatitis B virus vaccine are eligible.
• •19. Known seropositive for or active viral infection with hepatitis C virus (HCV), with the following exception: Subjects who had hepatitis C but have received an antiviral treatment and show no detectable viral ribonucleic acid (RNA) for 6 months are eligible.