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
- Compare the overall survival of patients with previously untreated stage I-III multiple
myelome treated with melphalan combined with dexamethasone or prednisone as induction
- 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.
- 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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Chaim Shustik, MD
Royal Victoria Hospital - Montreal
Canada: Health Canada
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