Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

• Progression-free survival [ Time Frame: From randomization to the earlier of progression or death of any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
  Tested using one-sided 0.95 confidence limits.
  
  
• Mean change of the FACT-Ntx TOI score (QOL) [ Time Frame: From registration to course 24 ] [ Designated as safety issue: No ]
  Differences between treatment arms are detected by 2-sample t-test, with 80% power, at a two-sided 0.05 significance level.
  
  

• Response rates (CR+VGPR+PR) [ Time Frame: Assessed up to 10 years ] [ Designated as safety issue: No ]
  Compared between arms using the Fisher's exact test.
  
  
• Overall survival [ Time Frame: Assessed up to 10 years ] [ Designated as safety issue: No ]
  Estimated using the method of Kaplan and Meier. Compared between the two arms using two-sided stratified log-rank test.
  
  
• Toxicity in terms of rates of grade 3 or higher SAE‟s on the two arms, graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. [ Time Frame: Assessed up to 10 years ] [ Designated as safety issue: Yes ]
  Compared using the Fisher's exact test.
  
  
• Impact of the differential treatment survival on QOL measured by FACT-Ntx TOI [ Time Frame: Assessed up to course 38 ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To compare progression-free survival between patients receiving melphalan, prednisone, and thalidomide versus melphalan, prednisone, and lenalidomide in newly diagnosed multiple myeloma patients who are not candidates for high-dose therapy.

SECONDARY OBJECTIVES:

I. To compare overall survival between both arms. II. To compare response rates and depth of response in these patients. III. To compare the incidence of toxicities in these patients. IV. To validate the TC classification of myeloma as a prognostic tool using gene expression profiling at diagnosis.

TERTIARY OBJECTIVES:

I. To compare quality-of-life (QOL) change between arms based on the FACT-Ntx TOI from baseline to the end of course 24 (maintenance therapy).

II. To examine the impact of differential treatment responses on QOL based on the FACT-Ntx TOI up to course 38.

III. To obtain prospective data on myeloma specific QOL attributes.

OUTLINE: This is a multicenter study. Patients are stratified according to ISS stage (I-II vs III) and age (< 65 vs ≥ 65). Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION THERAPY: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive oral thalidomide once daily and continue in the absence of disease progression.

ARM II:

INDUCTION THERAPY: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression.

Quality of life is assessed at baseline and periodically during treatment.

Peripheral blood and bone marrow samples are collected at baseline for gene expression profiling analysis.

After completion of study treatment, patients will be followed periodically for 10 years.