Combination Chemotherapy in Treating Patients With Multiple Myeloma
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.
|Multiple Myeloma and Plasma Cell Neoplasm||Drug: dexamethasone Drug: melphalan Drug: prednisone||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A COMPARATIVE STUDY OF DEXAMETHASONE VERSUS PREDNISONE (BOTH IN COMBINATION WITH MELPHALAN) AS INDUCTION THERAPY IN UNTREATED SYMPTOMATIC MYELOMA WITH AN ADDITIONAL ASSESSMENT OF DEXAMETHASONE VERSUS NO ADDITIONAL TREATMENT AS MAINTENANCE THERAPY IN NON-PROGRESSING PATIENTS|
- Overall survival [ Time Frame: 9 years ]
To compare overall survival between:
i) patients receiving melphalan-prednisone and those receiving melphalan-dexamethasone as induction therapy ii) patients maintained by dexamethasone and those on no additional treatment in the subgroup whose disease has not progressed at the time of the 12th induction cycle
- Time to progression [ Time Frame: 9 years ]
- Response rates [ Time Frame: 9 years ]
- Toxicity [ Time Frame: 9 years ]
- Quality of Life [ Time Frame: 9 years ]
|Study Start Date:||May 1995|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2003 (Final data collection date for primary outcome measure)|
Active Comparator: Melphan plus prednisone
melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; No treatment after stable response.
9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeksDrug: prednisone
100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan
Active Comparator: Melphan, prednisone pluse dexamethasone
melphalan plus prednisone qd x 4 28 day cycles x 12 cycles; dexamethasone qd x 4 q 28 days after non-progression
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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002678
Show 37 Study Locations
|Study Chair:||Chaim Shustik, MD||Royal Victoria Hospital - Montreal|