Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma

Inclusion Criteria

• •Disease related:
• •1. Symptomatic multiple myeloma
• •2. Relapsed or progressive disease after at least one but no more than three prior therapeutic treatments or regimens for multiple myeloma
• •3. Prior therapeutic treatment regimens may have included bortezomib, lenalidomide, and/or thalidomide, among other agents.
• •4. If previously treated with lenalidomide or bortezomib, the subject must not have progressed during the first 3 months of treatment with the drug and must not have discontinued treatment due to lenalidomide intolerance (bortezomib intolerant subjects may enroll).
• •5. Measurable disease, as indicated by one or more of the following:
• •* Serum M-protein ≥ 0.5 g/dL
• •* Urine Bence-Jones protein ≥ 200 mg/24 h
• •* If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with Immunoglobulin (Ig)A multiple myeloma), then quantitative immunoglobulin levels can be accepted.
• •6. Prior to enrollment, sites must provide evidence of myeloma progression/relapse, with start and stop dates of the most recent treatment regimen, as well as best tumor response to all prior treatment regimens.
• •Demographic
• •7. Males and females ≥ 18 years of age
• •8. Life expectancy of more than three months
• •9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• •Laboratory
• •10. Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) \< 3 times ULN
• •11. Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8 gm/dL, platelet count ≥ 50,000/ mm³ (≥ 30 × 10\^9/L if myeloma involvement in the bone marrow is \> 50%)
• •* Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks.
• •* Subjects may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
• •* Screening platelet count should be independent of platelet transfusions for at least 2 weeks
• •12. Calculated or measured creatinine clearance of ≥ 50 mL/minute, calculated using the formula of Cockcroft and Gault \[(140 - Age) x Mass (kg) / (72 x creatinine mg/dL)\]; multiply result by 0.85 (if female). Other generally accepted calculation methods can be substituted.
• •Ethical/Other
• •13. Written informed consent in accordance with federal, local, and institutional guidelines
• •14. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing
• •15. FCBP\* must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL within 10-14 days (US/RevAssist®) or 25 mIU/mL within 7-14 days (Canada/RevAidSM), prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or to use two methods of reliable birth control, including at least one highly effective method AND one additional effective method of birth control (contraception) AT THE SAME TIME, beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during therapy delay, and continuing for 4 weeks following discontinuation of lenalidomide therapy. If a hormonal method (birth control pills, injections, patch or implants) or intrauterine device (IUD) is not medically possible for the subject, the subject may use another highly effective method or two barrier methods AT THE SAME TIME.
• •16. Male subjects must agree to NEVER have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant, or he must use a latex condom EVERY TIME he engages in any sexual contact with females who are pregnant or may become pregnant while he is taking lenalidomide and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy. The subject must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks FOR ANY REASON, that his sexual partner may be pregnant.
• •17. Male subjects cannot donate semen or sperm while taking lenalidomide.
• •18. All study participants must be registered into the mandatory RevAssist (US) or RevAid (Canada) programs and be willing and able to comply with the requirements of Rev Assist/RevAid
• •19. Subjects must adhere to the study visit schedule and other protocol requirements and receive outpatient treatment and laboratory monitoring at the institute that administers the drug
• •20. Subjects must agree to take enteric-coated aspirin 81-325 mg orally daily, or if history of prior thrombotic disease or allergy to aspirin, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism.