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.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma	Drug: dexamethasone  Drug: melphalan  Drug: prednisone  Procedure: chemotherapy	Phase III

Further Study Details: 

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).

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven previously untreated stage I-III multiple myeloma
• Patients with stage I disease must be symptomatic
• Must meet at least 1 of the following conditions:
• Plasma cells in osteolytic lesion or soft tissue tumor biopsy
• At least 10% plasmacytosis in bone marrow aspirate and/or biopsy
• Less than 10% plasma cells in bone marrow but at least 1 bony lesion
• Detectable serum M-component of IgG, IgA, IgD, or IgE
• If only light chain disease (urine M-protein) present, urinary excretion of light chain (Bence Jones) protein must be at least 1.0 g/24 hours

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-4

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other concurrent serious illness
• Concurrent diabetes allowed, at the discretion of the treating physician, if changes in insulin requirements can be managed
• No other prior or concurrent malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent immunizations
• No concurrent filgrastim (G-CSF) or other growth factors as prophylaxis
• Concurrent epoetin alfa for anemia allowed

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior dexamethasone or prednisone with radiotherapy for spinal cord compression allowed if cumulative dexamethasone dose no greater than 120 mg and cumulative prednisone dose no greater than 792 mg
• Prior or concurrent corticosteroids for hypercalcemia allowed

Radiotherapy:

• See Endocrine therapy
• Prior focal radiotherapy allowed
• Concurrent focal radiotherapy during induction allowed
• Concurrent radiotherapy for palliation (e.g., painful osteolytic lesions or spinal cord compression) allowed

Surgery:

• At least 2 years since prior surgery for radiologic or endoscopic diagnosis of gastric or duodenal ulcer

Other:

• At least 2 years since prior medication for radiologic or endoscopic diagnosis of gastric or duodenal ulcer
• Prior or concurrent bisphosphonates for hypercalcemia allowed

Minnesota
      St. Mary's/Duluth Clinic Health System, Duluth,  Minnesota,  55805,  United States
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna,  British Columbia,  V1Y 5L3,  Canada
      British Columbia Cancer Agency - Vancouver Island Cancer Centre, Victoria,  British Columbia,  V8R 6V5,  Canada
      British Columbia Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
      Providence Health Care - Vancouver, Vancouver,  British Columbia,  V6Z 1Y6,  Canada
Canada, New Brunswick
      Doctor Leon Richard Oncology Centre, Moncton,  New Brunswick,  E1C 8X3,  Canada
      Moncton Hospital, Moncton,  New Brunswick,  E1C 6ZB,  Canada
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 2Y9,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario - Windsor Regional Cancer Centre, Windsor,  Ontario,  N8W 2X3,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Humber River Regional Hospital, Weston,  Ontario,  M9N 1N8,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Lakeridge Health Oshawa, Oshawa,  Ontario,  L1G 2B9,  Canada
      Northeastern Ontario Regional Cancer Centre, Sudbury, Sudbury,  Ontario,  P3E 5J1,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Southlake Regional Health Centre, Newmarket,  Ontario,  L3Y 2P9,  Canada
      St. Michael's Hospital - Toronto, Toronto,  Ontario,  M5B 1W8,  Canada
      Toronto East General Hospital, Toronto,  Ontario,  M4C 3E7,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
      Trillium Health Centre, Mississauga,  Ontario,  L5B 1B8,  Canada
      William Osler Health Centre, Brampton,  Ontario,  L6W 2Z8,  Canada
Canada, Prince Edward Island
      Queen Elizabeth Hospital, PEI, Charlottetown,  Prince Edward Island,  C1A 8T5,  Canada
Canada, Quebec
      CHUS-Hopital Fleurimont, Fleurimont,  Quebec,  J1H 5N4,  Canada
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada
      Hopital de L'Enfant Jesus, Quebec City,  Quebec,  G1J 1Z4,  Canada
      Hopital du Saint-Sacrement, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada

Study chairs or principal investigators

Chaim Shustik, MD,  Study Chair,  Royal Victoria Hospital - Montreal   

Study ID Numbers:  CDR0000064328; CAN-NCIC-MY7; NCI-V95-0713
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002678
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08