S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis
Condition: Multiple Myeloma; Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy such as melphalan work in different ways to stop cancer
      cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral
      stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and
      kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving melphalan together with autologous
      stem cell transplantation works in treating patients with multiple myeloma or primary
      systemic amyloidosis.
    

Detailed description: 
      OBJECTIVES:

        -  Determine overall survival of patients with high-risk multiple myeloma, primary systemic
           amyloidosis, or light chain deposition disease treated with two courses of modified
           high-dose melphalan and autologous peripheral blood stem cell transplantation.

        -  Determine the hematologic response in patients treated with this regimen.

        -  Determine the qualitative and quantitative toxic effects of this regimen in these
           patients.

        -  Determine the prognostic significance of cytogenetic markers in these patients.

      OUTLINE: This is a multicenter study. Patients are stratified according to disease (high-risk
      multiple myeloma vs primary systemic amyloidosis vs both).

        -  Induction therapy (multiple myeloma patients only): Patients receive oral dexamethasone
           on days 1-4, 9-12, and 17-20 and oral thalidomide daily on days 1-35. Treatment repeats
           every 35 days for 2 courses in the absence of disease progression or unacceptable
           toxicity.

        -  Mobilization and stem cell collection:

             -  Multiple myeloma patients: Within 28-35 days after completion of induction therapy,
                patients receive cyclophosphamide IV over 2-3 hours on day 1 and filgrastim (G-CSF)
                subcutaneously (SC) daily beginning on day 2 and continuing through the day before
                the last leukapheresis. Usage of mesna IV on day 1 (prior to and twice after
                cyclophosphamide administration is recommended).

             -  Primary systemic amyloidosis patients: Patients receive G-CSF SC daily beginning on
                day 1 and continuing through the day before the last leukapheresis.

      All patients undergo leukapheresis for the collection of stem cells until the target number
      of CD34+ cells is reached.

        -  Conditioning regimen: Within 1-4 weeks after mobilization, patients receive modified
           high-dose melphalan IV over 20 minutes on day -2.

        -  Peripheral blood stem cell (PBSC) reinfusion: PBSCs are reinfused on day 0. Patients
           receive G-CSF SC daily beginning on day 1 and continuing until blood counts recover.

      Patients undergo a second autologous PBSC transplantation within 3-6 months, but no later
      than 12 months, after the first transplantation.

        -  Second conditioning regimen: Patients receive modified high-dose melphalan IV over 20
           minutes on day -2.

        -  Second PBSC infusion: PBSCs are infused on day 0.

        -  Maintenance regimen (multiple myeloma patients only): Between 4-8 weeks after the second
           transplantation, patients with no progressive disease receive oral dexamethasone once
           daily on days 1-4 and oral thalidomide once daily on days 1-28. Courses repeat every 28
           days for 2 years in the absence of disease progression or unacceptable toxicity.

      Patients are followed at 3 and 6 months and then annually thereafter.

      PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 20-25
      months.
    

Intervention name(s): filgrastim; cyclophosphamide; dexamethasone; melphalan; thalidomide; peripheral blood stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primary systemic amyloidosis; stage II multiple myeloma; stage III multiple myeloma