Combination Chemotherapy in Treating Patients With Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

Comparative Study of Dexamethasone vs Prednisone (Both in Combination With Melphalan) as Induction Therapy in Untreated Symptomatic Myeloma With an Additional Assessment of Dexamethasone vs no Additional Treatment as Maintenance Therapy in Non-Progressing Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002678
• Other study ID #: MY7
• Secondary ID: CAN-NCIC-MY7NCI-
• Status: Completed
• Phase: Phase 3
• Start date: June 2, 1995
• Est. completion date: December 21, 2009

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 595
• Est. completion date: December 21, 2009
• Est. primary completion date: May 3, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• dexamethasone
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.
• melphalan
9 mg/m2 daily for 4 days given orally on an empty stomach every 4 weeks
• prednisone
100 mg daily for 4 days given orally on a full stomach with each cycle of melphalan

Locations

Country	Name	City	State
Canada	William Osler Health Centre	Brampton	Ontario
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Queen Elizabeth Hospital, PEI	Charlottetown	Prince Edward Island
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUS-Hopital Fleurimont	Fleurimont	Quebec
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	Doctor Leon Richard Oncology Centre	Moncton	New Brunswick
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	McGill University	Montreal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Hopital de L'Enfant Jesus	Quebec City	Quebec
Canada	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Algoma District Medical Group	Sault Sainte Marie	Ontario
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador
Canada	Northeastern Ontario Regional Cancer Centre, Sudbury	Sudbury	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Canada	Providence Health Care - Vancouver	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Humber River Regional Hospital	Weston	Ontario
Canada	Cancer Care Ontario - Windsor Regional Cancer Centre	Windsor	Ontario
United States	St. Mary's/Duluth Clinic Health System	Duluth	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Shustik C, Belch A, Meyer R, et al.: Melphalan-dexamethasone is not superior to melphalan-prednisone as induction therapy in multiple myeloma. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1191, 2001.

Shustik C, Belch A, Robinson S, et al.: Dexamethasone (dex) maintenance versus observation (obs) in patients with previously untreated multiple myeloma: a National Cancer Institute of Canada Clinical Trials Group study: MY.7. [Abstract] J Clin Oncol 22 (S

Shustik C, Belch A, Robinson S, Rubin SH, Dolan SP, Kovacs MJ, Grewal KS, Walde D, Barr R, Wilson J, Gill K, Vickars L, Rudinskas L, Sicheri DA, Wilson K, Djurfeldt M, Shepherd LE, Ding K, Meyer RM. A randomised comparison of melphalan with prednisone or — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	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	9 years
Secondary	Time to progression		9 years
Secondary	Response rates		9 years
Secondary	Toxicity		9 years
Secondary	Quality of Life		9 years