Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma
Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma
This study is to determine whether addition of Revlimid to standard therapy will increase
 overall and complete response rates compared to historical standard frontline therapy and
 whether this combination treatment has fewer side effects than similar combination induction
 treatment.
Current multiple myeloma therapies, typically an induction regimen followed by consolidation
 therapy with high dose chemotherapy and autologous stem cell rescue (autologous
 transplantation), can induce remission but relapse and death are inevitable. A growing body
 of literature suggests that consolidation therapy with autologous transplantation does not
 confer additional survival benefit and may have increased procedure-related morbidity and
 mortality in patients over 65 years old. Autologous transplantation is no longer recommended
 as standard care for this population. In addition, certain patients may not be eligible for
 autologous transplantation due to co-morbid medical conditions or may elect not to undergo
 the procedure for personal reasons.

 The historic standard of care for multiple myeloma patients who were not eligible for
 autologous transplantation for consolidation was induction therapy with melphalan/ prednisone
 (MP), often followed by some form of maintenance therapy after achievement of complete or
 partial remission. A recent phase 3 study showed that the addition of thalidomide to MP (MPT)
 demonstrated higher overall and complete response rates. For patients who are eligible for
 autologous transplantation, thalidomide/ dexamethasone (Thal Dex) induction therapy is
 considered the standard of care, but a phase 2 study of lenalidomide (Revlimid)/
 dexamethasone (Rev Dex) induction therapy demonstrated higher overall and complete response
 rates compared to Thal Dex. In addition, lenalidomide has a favorable side effect profile
 compared to thalidomide. Based on these data, we hypothesize that the combination of
 Revlimid/ melphalan/ dexamethasone (ReMeDex) induction therapy for myeloma patients who are
 not planned for autologous transplantation due to age restriction or other factors may
 demonstrate higher overall and/ or complete response rates with fewer side effects.
Inclusion Criteria:

 -  Newly Diagnosed multiple myeloma, ISS stage I-III requiring therapy: Serum M-protein
 ≥1 gm/dL (≥10 gm/L), Urine M-protein ≥200 mg/24 hr, Serum FLC assay: involved FLC ≥10
 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal

 -  Previously untreated except prior treatment with corticosteroid less than one full
 cycle of pulsed dose dexamethasone (40 mg daily days 1-4, 9-12, and 17-20) or
 equivalent is allowed. Concomitant administration of IV bisphosphonates, Zometa
 (zoledronic acid, up to 4 mg IVSS over 30 minutes every four weeks) or Aredia
 (alendronate, up to 90 mg IVSS over 4 hours every four weeks), for prophylaxis against
 skeletal complications due to lytic bone disease or for acute management of
 hypercalcemia is allowed. Concomitant external beam radiation therapy for local
 management of lytic bone disease is allowed.

 -  Age ≥ 18 years old

 -  Life expectancy ≥ 12 weeks

 -  Eastern Cooperative Oncology Group (ECOG) Performance Status will be employed. ECOG
 0-2 accepted.

 -  WBC ≥ 3.0 X 103/ µL, ANC ≥ 1.5 X 103/ µl, Hgb ≥ 8.0 gm/ dL, Plt ≥ 75 X 103/ µl, Serum
 Creatinine ≤ 2.0 mg/ dL

 -  Ability to understand and the willingness to sign a written informed consent document.

 -  All study participants must be registered into the mandatory RevAssist® program, and
 be willing and able to comply with the requirements of RevAssist®.

 -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
 test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
 within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7
 days) and must either commit to continued abstinence from heterosexual intercourse or
 begin TWO acceptable methods of birth control, one highly effective method and one
 additional effective method AT THE SAME TIME, at least 28 days before she starts
 taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree
 to use a latex condom during sexual contact with a FCBP even if they have had a
 successful vasectomy. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing
 Guidelines and Acceptable Birth Control Methods.

 -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
 intolerant to ASA may use warfarin or low molecular weight heparin).

 Exclusion Criteria:

 -  Prior therapy with Revlimid®, Thalomid (thalidomide), Velcade (bortezomib), Alkeran
 (melphalan) excluded. Prior therapy with corticosteroid allowed as defined in
 inclusion criteria.

 -  No prior or concurrent treatment with an investigational agent.

 -  Active Hepatitis B or C excluded, New York Heart Association grade III/IV congestive
 heart failure excluded, History of bleeding disorder excluded, History of platelet
 function disorder, History of deep vein thrombosis or other thromboembolic event
 excluded

 -  Prior history of allergic reaction to IMiD™ compounds (Thalidomide, Lenalidomide)
 excluded.

 -  Concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs)(with the
 exception of aspirin) or other nephrotoxic agents is excluded.

 -  Serum creatinine > 2.0 mg/ dL is excluded

 -  Pregnancy and breastfeeding excluded

 -  Known HIV+ patients are excluded.

 -  Other active hematologic or solid tumor or history of such disease requiring therapy
 of any form within five years of screening is excluded.