Clinical trial NCT00002678: Combination Chemotherapy in Treating Patients With Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 595
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility 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

Primary outcomes:
measure: Overall survival
timeFrame: 9 years
Secondary outcomes:
measure: Time to progression
timeFrame: 9 years
measure: Response rates
timeFrame: 9 years
measure: Toxicity
timeFrame: 9 years
measure: Quality of Life
timeFrame: 9 years
Other outcomes:
Locations:
city: Duluth
country: United States
facility: St. Mary's/Duluth Clinic Health System
state: Minnesota
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Vancouver
country: Canada
facility: Providence Health Care - Vancouver
state: British Columbia
city: Victoria
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Cancer Centre
state: British Columbia
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Moncton
country: Canada
facility: Doctor Leon Richard Oncology Centre
state: New Brunswick
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Brampton
country: Canada
facility: William Osler Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Sault Sainte Marie
country: Canada
facility: Algoma District Medical Group
state: Ontario
city: St. Catharines
country: Canada
facility: Hotel Dieu Health Sciences Hospital - Niagara
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre, Sudbury
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital
state: Ontario
city: Windsor
country: Canada
facility: Cancer Care Ontario - Windsor Regional Cancer Centre
state: Ontario
city: Charlottetown
country: Canada
facility: Queen Elizabeth Hospital, PEI
state: Prince Edward Island
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Hopital de L'Enfant Jesus
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint-Sacrement, Quebec
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Royal Victoria Hospital - Montreal
name: Chaim Shustik, MD
role: STUDY_CHAIR
References:
citation: 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 dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7. Br J Haematol. 2007 Jan;136(2):203-11. doi: 10.1111/j.1365-2141.2006.06405.x.
citation: 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 (Suppl 14): A-6510, 560s, 2004.
citation: 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.