Lenalidomide and Melphalan in Treating Patients With Previously Untreated Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the
      cancer. It may also stimulate the immune system in different ways and stop cancer cells from
      growing. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the
      growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving
      lenalidomide together with melphalan may kill more cancer cells.

      PURPOSE: This randomized phase II trial is studying the side effects and best dose of
      lenalidomide when given together with melphalan and to see how well they work in treating
      patients with multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the tolerability of 2 different doses of lenalidomide when administered with
           melphalan in patients with previously untreated multiple myeloma who are not planning to
           undergo future autologous stem cell transplantation.

      Secondary

        -  Characterize the toxicity profile of lenalidomide in combination with melphalan.

        -  Determine tumor response in these patients after 2 and 12 courses of induction therapy
           with lenalidomide and melphalan and after 6 months of maintenance therapy with
           dexamethasone.

        -  Determine progression-free and overall survival of these patients.

        -  Determine time to dose modification and time to dose discontinuation in these patients.

      Tertiary

        -  Examine wnt pathway inhibition in response to lenalidomide on pre- and post-treatment
           bone marrow and blood samples using enzyme-linked immunosorbent assay (ELISA), gene
           expression profiling, drosophila-based chemical genetics, and surface-enhanced laser
           desorption/ionization mass spectrometry (SELDI MS) proteomics.

      OUTLINE: This is a multicenter, randomized, open-label, dose-finding study of lenalidomide.

      Prior to randomization, 6 patients receive oral lenalidomide at a lower dose (same dose to be
      used in arm I) once daily on days 1-21 and oral melphalan once daily on days 1-4. Treatment
      repeats every 28 days for 3 courses. If no unacceptable toxicity occurs, the trial will
      proceed and randomization will occur.

        -  Induction therapy: Patients are randomized to 1 of 2 dose levels of lenalidomide.

             -  Arm I: Patients receive oral lenalidomide once daily on days 1-21 and oral
                melphalan once daily on days 1-4.

             -  Arm II: Patients receive oral lenalidomide as in arm I, but at a lower dose, and
                melphalan as in arm I, but at a higher dose.

      Treatment in both arms repeats every 28 days for up to 12 courses in the absence of disease
      progression or unacceptable toxicity. After 12 courses of induction therapy, patients in both
      arms without progressive disease proceed to maintenance therapy.

        -  Maintenance therapy: Patients receive oral dexamethasone once daily on days 1-4. Courses
           repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed at 4 weeks and then every 2 months
      thereafter.

      PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
    

Intervention name(s): dexamethasone; lenalidomide; melphalan
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Dexamethasone; Lenalidomide; Melphalan
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma