• Patients With Overall Confirmed Response [ Time Frame: Every cycle during treatment ] [ Designated as safety issue: No ]

  Response that was confirmed on 2 consecutive evaluations.

  • Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and <=5% plasma cells in bone marrow
  • Very Good Parital Response (VGPR): >=90% reduction in serum M-spike, Urine M-spike <100mg per 24 hours
  • Partial Response (PR): >=50% reduction in serum M-spike, Urine M-spike >=90% reduction or < 200mg per 24 hours, or >=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells
  
  

• Time to Progression (TTP) [ Time Frame: registration to progressive disease (up to 3 years) ] [ Designated as safety issue: No ]
  TTP was defined as the time from registration to disease progression. Patients who died were considered to have disease progression at time of death unless documented evidence clearly indicates no progression has occurred
  
  
• Overall Survival (OS) [ Time Frame: registration to death (up to 3 years) ] [ Designated as safety issue: No ]
  OS was defined as the time from registration to death due to any cause. Patients who were alive were censored at date of last follow-up.
  
  
• Duration of Response (DOR) [ Time Frame: from first response to progression or death (up to 3 years) ] [ Designated as safety issue: No ]
  Duration of response was calculated from documentation of first response to date of progression in the subset of patients who responded. Patients without progression were censored at the date of last tumor evaluation.
  
  
• Patients With Grade 3 or Higher Adverse Events [ Time Frame: Every cycle during treatment ] [ Designated as safety issue: Yes ]
  Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.
  
  

Drug: lenalidomide

Phase I - dose escalating: 5mg level -1, 10mg level 0, 10mg level 1, 15mg level 2, 20mg level 3, 25mg level 4, orally days 1-21 every 28 days until progression

Phase II - 10 mg orally days 1-21 every 28 days until progression

Drug: melphalan

Phase I - dose escalating: 5mg/m^2 dose level -1, 5 mg/m^2 dose level 0, 8 mg/m^2 dose level 1 - 4, daily x 4 orally days every 28 days until progression

Phase II - 5mg/m^2 orally days 1-4 every 28 days until progression

Drug: prednisone
60mg/m^2, orally days 1-4 every 28 days until progression

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of melphalan and lenalidomide in combination with prednisone in patients with newly diagnosed multiple myeloma.
• Determine the response rate in patients treated with this regimen. Secondary
• Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study of melphalan and lenalidomide followed by a phase II study.
• Phase I: Patients receive oral melphalan and oral prednisone daily on days 1-4. Patients also receive oral lenalidomide daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of melphalan and lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase II: Patients receive oral melphalan and oral lenalidomide as in phase I at the MTD. Patients also receive oral prednisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years.