Combination Chemotherapy With or Without PSC 833 in Treating Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining PSC 833 with chemotherapy may reduce resistance to the drug, and allow more tumor cells to be killed. It is not yet known whether combination chemotherapy plus PSC 833 is more effective than combination chemotherapy alone in treating patients with relapsed or refractory multiple myeloma.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 in treating patients with relapsed or refractory multiple myeloma.
|Multiple Myeloma and Plasma Cell Neoplasm||Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: valspodar Drug: vincristine sulfate||Phase 3|
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||A PHASE III STUDY OF PSC-833 IN COMBINATION WITH VINCRISTINE, DOXORUBICIN AND DEXAMETHASONE (PSC-833/VAD) VERSUS VAD ALONE IN PATIENTS WITH RELAPSING OR REFRACTORY MULTIPLE MYELOMA|
|Study Start Date:||March 1997|
|Primary Completion Date:||April 2003 (Final data collection date for primary outcome measure)|
- Compare the overall survival and objective response rate of patients with relapsed or refractory multiple myeloma treated with vincristine, doxorubicin, and dexamethasone (VAD) with or without PSC 833.
- Compare event free survival and subjective response in patients treated with these regimens.
- Correlate treatment outcome with p-glycoprotein expression.
- Determine whether prognostic factors previously determined to be useful in untreated patients (i.e., plasma cell labeling index and multidrug resistance determined from bone marrow aspirates, serum beta 2-microglobulin and interleukin-6 receptor levels) correlate with objective and subjective response and event-free and overall survival in patients treated with these regimens.
- Compare the toxicity of VAD with or without PSC 833.
OUTLINE: This is a randomized, multicenter study. Patients are stratified by response to prior treatment, prior doxorubicin and/or vincristine, prior autologous peripheral blood stem cell transplantation, and center.
Patients are randomized to 1 of 2 treatment arms:
- Arm I: The first group receives vincristine, doxorubicin, and dexamethasone (VAD). Patients receive higher dose vincristine IV over 96 hours and higher dose doxorubicin IV over 96 hours on days 1-4 and oral dexamethasone daily on days 1-4 and 15-18.
- Arm II: The second group receives VAD plus oral PSC 833. Patients receive oral PSC 833 every 6 hours beginning on day 1 and continuing for 20 doses. Patients receive lower dose vincristine IV over 96 hours and lower dose doxorubicin IV over 96 hours on days 2-5 and oral dexamethasone daily on days 2-5 and 16-19.
Treatment in both arms repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of 2 courses, patients are reevaluated, and those with stable or responding disease continue treatment for 2 courses beyond maximum response. Doxorubicin is discontinued in patients who receive a maximum lifetime dose but still have stable or responding disease.
Patients are followed every 2 months for survival.
PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study over approximately 20 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002878
Show 40 Study Locations
|Study Chair:||William R. Friedenberg, MD||Guthrie Cancer Center at Guthrie Clinic Sayre|
|Study Chair:||Karl H. Hanson, MD||Saint Luke's Cancer Institute at Saint Luke's Hospital|
|Study Chair:||Richard A. Larson, MD||University of Chicago|
|Study Chair:||Chaim Shustik, MD||Royal Victoria Hospital - Montreal|
|Study Chair:||Pieter Sonneveld, MD, PhD||University Medical Center Rotterdam at Erasmus Medical Center|