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
- 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
- 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
Allocation: Randomized, Primary Purpose: Treatment
William R. Friedenberg, MD
Guthrie Cancer Center at Guthrie Clinic Sayre
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Walter Reed Army Medical Center||Washington, District of Columbia 20307-5000|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|University of Massachusetts Memorial Medical Center||Worcester, Massachusetts 01655|
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|
|Lineberger Comprehensive Cancer Center, UNC||Chapel Hill, North Carolina 27599-7295|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Rhode Island Hospital||Providence, Rhode Island 02903|
|Vermont Cancer Center||Burlington, Vermont 05401-3498|
|CCOP - Southern Nevada Cancer Research Foundation||Las Vegas, Nevada 89106|
|University of California San Diego Cancer Center||La Jolla, California 92093-0658|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - Mount Sinai Medical Center||Miami Beach, Florida 33140|
|Marlene & Stewart Greenebaum Cancer Center, University of Maryland||Baltimore, Maryland 21201|
|Ellis Fischel Cancer Center - Columbia||Columbia, Missouri 65203|
|Barnes-Jewish Hospital||Saint Louis, Missouri 63110|
|Norris Cotton Cancer Center||Lebanon, New Hampshire 03756|
|CCOP - North Shore University Hospital||Manhasset, New York 11030|
|State University of New York - Upstate Medical University||Syracuse, New York 13210|
|CCOP - Southeast Cancer Control Consortium||Winston-Salem, North Carolina 27104-4241|
|University of Tennessee, Memphis Cancer Center||Memphis, Tennessee 38103|
|MBCCOP - Massey Cancer Center||Richmond, Virginia 23298-0037|
|Mount Sinai Medical Center, NY||New York, New York 10029|
|New York Presbyterian Hospital - Cornell Campus||New York, New York 10021|
|Holden Comprehensive Cancer Center at The University of Iowa||Iowa City, Iowa 52242-1009|
|Comprehensive Cancer Center at Wake Forest University||Winston-Salem, North Carolina 27157-1082|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.||Syracuse, New York 13217|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Schneider Children's Hospital at North Shore||Manhasset, New York 11030|