Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant

Inclusion Criteria

• •Age 18 years and ≤ 80 years
• •High risk smoldering myeloma, which is untreated, as defined by either of the two following criteria:
• •1. Presence of any two of the following: Serum M spike \> 2 gm/dL OR an involved to uninvolved free light chain (FLC) ratio \> 20 OR bone marrow PC% \> 20%
• •2. Total score of 9 or above using the following scoring system:
• •FLC Ratio \>10-25 = 2 \>25-40 = 3 \> 40 = 5
• •Serum M Protein (g/dL) \>1.5-3 = 3 \>3 = 4
• •BMPC% \>15-20 = 2 \>20-30 = 3 \>30-40 = 5 \>40 = 6
• •FISH abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2
• •The following laboratory values obtained 14 days prior to registration.
• •Calculated creatinine clearance (using Cockcroft-Gault equation below)\* ≥ 30 mL/min
• •Absolute neutrophil count (ANC) ≥ 1000/mm3 (without the use of growth factors)
• •Platelet count ≥ 75000/mm3
• •Hemoglobin ≥8.0 g/dL
• •Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• •alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
• •left ventricular ejection fraction (LVEF) ≥ 40%
• •LVEF ≥ 40%
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Appendix VII)
• •Previously untreated.
• •Provide informed written consent.
• •Negative pregnancy test done ≤14 days prior to cycle 1 day 1, for women of childbearing potential only.
• •All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of the REMS® program.
• •Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
• •Willing to follow strict birth control measures as outlined in the protocol.
• •Female subjects: If they are of childbearing potential, agree to one of the following:
• •Practice 2 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 trial drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
• •Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• •Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
• •Agree to practice effective barrier contraception during the entire trial treatment period and through 90 days after the last dose of trial drug, OR
• •Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
• •Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• •* Willing to return to enrolling institution for follow-up during the Active Treatment Phase of the trial.
• •* Male subjects must agree not to donate sperm for at least 90 days after the last dose of study treatment.
• •* Willing to provide samples for planned research
• •* Life expectancy \> 6 months
• •* Able to take aspirin (325 mg) daily as prophylactic anticoagulation. Subjects intolerant to aspirin may use warfarin or low dose molecular weight heparin, novel oral anticoagulants, or low dose molecular weight heparin