Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Multiple Myeloma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	Other	CAN-NCIC-MY7 NCI-V95-0713, NCT00002678, MY7

Objectives

1. 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.
2. Compare the overall survival of patients with stable or responding disease after induction treated with dexamethasone vs observation alone as maintenance therapy.
3. Compare the time to progression, response rate, and quality of life of patients treated with these regimens.
4. Compare the toxic effects of these regimens in these patients.

Entry 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

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

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

Expected Enrollment

A maximum of 600 patients will be accrued for this study within 6 years.

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.

Shustik C, Belch A, Robinson S, et al.: 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 136 (2): 203-11, 2007.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Chaim Shustik, MD, Protocol chair		Ph: 514-398-1444 Email: shustikc@muhchem.mcgill.ca

Registry Information
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
Trial Start Date		1995-05-18
Registered in ClinicalTrials.gov		NCT00002678
Date Submitted to PDQ		1995-05-18
Information Last Verified		2000-11-29