Combination Chemotherapy in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	NCIC Clinical Trials Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002678

Purpose

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	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone Drug: melphalan Drug: prednisone	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Prednisone Dexamethasone acetate Doxiproct plus Melphalan Sarcolysin Dexamethasone Sodium Phosphate Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	600
Study Start Date:	May 1995

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002678

Hide Study Locations

Locations

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

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

Study Chair:

Chaim Shustik, MD

Royal Victoria Hospital - Montreal

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

Study ID Numbers:	CDR0000064328, CAN-NCIC-MY7, NCI-V95-0713
Study First Received:	November 1, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00002678 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Prednisone
Melphalan
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Hemostatic Disorders
Hormones
Hemorrhagic Disorders

Therapeutic Uses
Cardiovascular Diseases
Alkylating Agents
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Gastrointestinal Agents
Vascular Diseases
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Multiple Myeloma

ClinicalTrials.gov processed this record on November 27, 2009