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
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
- Response rates [ Time Frame: 9 years ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
- Quality of Life [ Time Frame: 9 years ] [ Designated as safety issue: No ]
|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.
Hide Study Locations
|United States, Minnesota|
|St. Mary's/Duluth Clinic Health System|
|Duluth, Minnesota, United States, 55805|
|Tom Baker Cancer Center - Calgary|
|Calgary, Alberta, Canada, T2N 4N2|
|Cross Cancer Institute|
|Edmonton, Alberta, Canada, T6G 1Z2|
|Canada, British Columbia|
|British Columbia Cancer Agency - Centre for the Southern Interior|
|Kelowna, British Columbia, Canada, V1Y 5L3|
|Providence Health Care - Vancouver|
|Vancouver, British Columbia, Canada, V6Z 1Y6|
|British Columbia Cancer Agency|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|British Columbia Cancer Agency - Vancouver Island Cancer Centre|
|Victoria, British Columbia, Canada, V8R 6V5|
|Canada, New Brunswick|
|Doctor Leon Richard Oncology Centre|
|Moncton, New Brunswick, Canada, E1C 8X3|
|Moncton, New Brunswick, Canada, E1C 6ZB|
|Saint John Regional Hospital|
|Saint John, New Brunswick, Canada, E2L 4L2|
|Canada, Newfoundland and Labrador|
|Newfoundland Cancer Treatment and Research Foundation|
|St. Johns, Newfoundland and Labrador, Canada, A1B 3V6|
|Canada, Nova Scotia|
|Nova Scotia Cancer Centre|
|Halifax, Nova Scotia, Canada, B3H 2Y9|
|William Osler Health Centre|
|Brampton, Ontario, Canada, L6W 2Z8|
|Cancer Care Ontario-Hamilton Regional Cancer Centre|
|Hamilton, Ontario, Canada, L8V 5C2|
|Kingston Regional Cancer Centre|
|Kingston, Ontario, Canada, K7L 5P9|
|Cancer Care Ontario-London Regional Cancer Centre|
|London, Ontario, Canada, N6A 4L6|
|Credit Valley Hospital|
|Mississauga, Ontario, Canada, L5M 2N1|
|Trillium Health Centre|
|Mississauga, Ontario, Canada, L5B 1B8|
|Southlake Regional Health Centre|
|Newmarket, Ontario, Canada, L3Y 2P9|
|Lakeridge Health Oshawa|
|Oshawa, Ontario, Canada, L1G 2B9|
|Algoma District Medical Group|
|Sault Sainte Marie, Ontario, Canada, P6B 1Y5|
|Hotel Dieu Health Sciences Hospital - Niagara|
|St. Catharines, Ontario, Canada, L2R 5K3|
|Northeastern Ontario Regional Cancer Centre, Sudbury|
|Sudbury, Ontario, Canada, P3E 5J1|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|St. Michael's Hospital - Toronto|
|Toronto, Ontario, Canada, M5B 1W8|
|Toronto East General Hospital|
|Toronto, Ontario, Canada, M4C 3E7|
|Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2C4|
|Toronto Sunnybrook Regional Cancer Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|Humber River Regional Hospital|
|Weston, Ontario, Canada, M9N 1N8|
|Cancer Care Ontario - Windsor Regional Cancer Centre|
|Windsor, Ontario, Canada, N8W 2X3|
|Canada, Prince Edward Island|
|Queen Elizabeth Hospital, PEI|
|Charlottetown, Prince Edward Island, Canada, C1A 8T5|
|Fleurimont, Quebec, Canada, J1H 5N4|
|Hopital Charles Lemoyne|
|Greenfield Park, Quebec, Canada, J4V 2H1|
|Montreal, Quebec, Canada, H2W 1S6|
|Hopital du Saint-Sacrement, Quebec|
|Quebec City, Quebec, Canada, G1S 4L8|
|Hopital de L'Enfant Jesus|
|Quebec City, Quebec, Canada, G1J 1Z4|
|Allan Blair Cancer Centre|
|Regina, Saskatchewan, Canada, S4T 7T1|
|Study Chair:||Chaim Shustik, MD||Royal Victoria Hospital - Montreal|