Combination Chemotherapy in Treating Patients With Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining more than one drug may kill more tumor cells. It is not
      yet known which combination chemotherapy regimen is most effective in treating patients with
      multiple myeloma.

      PURPOSE: Randomized phase III trial to compare the effectiveness of various combination
      chemotherapy regimens in treating patients with multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the overall survival of patients with previously untreated stage I-III multiple
           myelome treated with melphalan combined with dexamethasone or prednisone as induction
           therapy.

        -  Compare the overall survival of patients with stable or responding disease after
           induction treated with dexamethasone vs observation alone as maintenance therapy.

        -  Compare the time to progression, response rate, and quality of life of patients treated
           with these regimens.

        -  Compare the toxic effects of these regimens in these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, stage (I
      or II vs III), creatinine (less than 2.0 mg/dL vs 2.0 mg/dL or greater), and intention to use
      prophylactic bisphosphonate (yes vs no).

        -  Induction: Patients are randomized to 1 of 4 treatment arms.

             -  Arms I and II: Patients receive induction comprising oral prednisone followed by
                oral melphalan on days 1-4.

             -  Arms III and IV: Patients receive induction comprising oral melphalan and oral
                dexamethasone (DM) on days 1-4 of all courses and DM on days 15-18 of courses 1-3.

      Induction for arms I-IV continues every 4 weeks for 12 courses in the absence of disease
      progression or unacceptable toxicity. Patients with stable or responding disease after
      induction proceed to maintenance therapy.

        -  Maintenance:

             -  Arms I and III: Patients undergo observation.

             -  Arms II and IV: Patients receive oral DM on days 1-4. Maintenance therapy continues
                every 4 weeks for arms II and IV and every 3 months for arms I and III in the
                absence of disease progression or unacceptable toxicity. Patients on arms I-IV who
                develop disease progression proceed to reinduction.

        -  Reinduction: Patients restart induction on the arm to which they were originally
           randomized. Reinduction continues every 4 weeks in the absence of stable response
           lasting 16 weeks, disease progression, or unacceptable toxicity. Patients who achieve a
           stable response lasting 16 weeks restart maintenance therapy. Patients who experience
           further disease progression during reinduction are taken off study.

      Quality of life is assessed at baseline, on day 1 of courses 1-3 and then every 3 courses
      during induction, and then every 3 months during maintenance therapy.

      Patients are followed every 6 months.

      PROJECTED ACCRUAL: A maximum of 600 patients will be accrued for this study within 6 years.
    

Intervention name(s): dexamethasone; melphalan; prednisone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 40 mg daily for four days given orally and repeated every 28 days should commence on day 29 of the twelfth cycle of induction therapy.; 9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeks; 100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan
Intervention MeSH terms: Dexamethasone; Prednisone; Melphalan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma