NCT00002878

Combination Chemotherapy With or Without PSC 833 in Treating Patients With Relapsed or Refractory Multiple Myeloma

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: —
• Sponsor: Eastern Cooperative Oncology Group · Network
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

OBJECTIVES: * 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.

Conditions

• Multiple Myeloma and Plasma Cell Neoplasm

Interventions

Type	Name	Description
DRUG	dexamethasone
DRUG	doxorubicin hydrochloride
DRUG	valspodar
DRUG	vincristine sulfate

Timeline

• Start date: 1997-06-30
• Primary completion: 2003-04-01
• First posted: 2003-07-09
• Last updated: 2023-06-15

Locations

40 sites across 2 countries: United States, Canada