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

NCT00002878 | Completed Phase 3

• 9 other identifiers: CDR0000065178E-1A95CAN-NCIC-MY8CLB-E1A95EORTC-E1A95/06971SWOG-E1A95CAN-NCIC-J1A95CLB-9596SWOG-S1A95
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 40

Brief 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

refractory multiple myeloma

Interventions

dexamethasone DRUG

doxorubicin hydrochloride DRUG

valspodar DRUG

vincristine sulfate DRUG

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Multiple myeloma of any stage confirmed by: * Bone marrow plasmacytosis with at least 10% plasma cells, sheets of plasma cells, or biopsy proven plasmacytosis * Myeloma (M) protein in serum and/or urine * Measurable disease by at least one of the following: * Serum M-component at least 1.0 g/dL by electrophoresis * Baseline measurement by nephelometry also, if used to follow response * Urine M-protein excretion greater than 200 mg/24 hours by electrophoresis * The following are not considered measurable but are followed for response: * Lytic bone lesions * Bone marrow plasmacytosis * Anemia * Serum beta 2-microglobulin * Objective evidence of progression by at least one of the following: * Increased serum M-protein (by electrophoresis unless M-spike less than 1.5 g/dL) * At least 50% above lowest remission level or by at least 2 g/dL * To more than 1.0 g/dL if sole protein indication of relapse * Nephelometry may be used instead of electrophoresis * Increased urine M-protein * To 50% above lowest level OR by 2 g/24 hours * To greater than 200 mg/24 hours * Definite new lytic bone lesions or at least a 50% increase in size of existing lesions (discussion with ECOG Study Chairman required if sole indication of progression) * Increase in serum or urine M-protein by 25% to under 50% (as above) plus one of the following: * Serum calcium greater than 12 mg/dL without other cause * Hemoglobin decreased by more than 2.0 g/dL not attributed to chemotherapy, interferon therapy, or a myelodysplastic syndrome * Less than 11 g/dL in men * Less than 10 g/dL in women * At least a 50% increase in bone marrow plasmacytosis * Failure of prior cytotoxic therapy defined by one of the following: * Never responded * Relapsed within 2 months of last treatment * Relapsed 2-12 months after last treatment following initial response * Adequate prior chemotherapy required, e.g.: * At least 2 courses of combination chemotherapy (e.g., VBMCP, VBAP, MP) * Prior vincristine, doxorubicin, and dexamethasone (VAD) allowed * No demonstrated resistance to VAD * At least 3 months since prior VAD * Cumulative doxorubicin dose no more than 250 mg/m2 * Prior autologous peripheral blood stem cell transplant allowed if performed prior to development of drug resistance * No prior allogeneic transplant * No smoldering myeloma, localized plasmacytoma, or monoclonal gammopathy of undetermined significance (MGUS) PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-3 Life expectancy: * At least 2 months Hematopoietic: * Absolute neutrophil count at least 1,000/mm\^3 * Platelet count at least 50,000/mm\^3 Hepatic: * Bilirubin less than 1.5 times upper limit of normal (ULN) * AST less than 1.5 times ULN * No chronic or active hepatitis or cirrhosis Renal: * Creatinine less than 3.0 mg/dL Cardiovascular: * Ejection fraction at least 50% * No history of congestive heart failure * No overt angina despite medication * No myocardial infarction within 2 months * No poorly controlled hypertension (i.e., pressure 200/110 or higher despite medication) * No arrhythmia requiring therapy (i.e., sustained atrial or ventricular arrhythmia or multifocal premature ventricular contraction) * Digoxin to control ventricular rate of atrial fibrillation that has been chronic for more than 1 month allowed Neurologic: * No peripheral neuropathy with weakness * No cerebellar disease with ataxia Gastrointestinal: * Adequate gastrointestinal function to allow absorption of PSC 833 * No active peptic ulcer Other: * No hypersensitivity to PSC 833 or cyclosporine * No active infection * HIV negative * No uncontrolled diabetes mellitus * No second malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other localized cancer treated with surgery alone * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other serious medical problem unless sufficiently stabilized PRIOR CONCURRENT THERAPY: Biologic therapy: * Prior biologic therapy (e.g., interferon) allowed Chemotherapy: * See Disease Characteristics * At least 3 weeks since other prior chemotherapy (including plicamycin) Endocrine therapy: * At least 2 weeks since high dose steroids (at least 100 mg/m2/day of prednisone or at least 40 mg/day of dexamethasone (including steroids for hypercalcemia) Radiotherapy: * At least 2 weeks since prior radiotherapy except limited radiotherapy to a single bone lesion Surgery: * At least 4 weeks since prior major surgery Other: * No concurrent anticoagulants * No concurrent drugs known to modulate cyclosporine blood concentrations

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• SWOG Cancer Research Network: collaborator
• Cancer and Leukemia Group B: collaborator
• NCIC Clinical Trials Group: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (40)

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94143-0128, United States

Location

CCOP - Christiana Care Health Services

Wilmington, Delaware, 19899, United States

Location

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5000, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, 52242-1009, United States

Location

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, 65203, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3330, United States

Location

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Schneider Children's Hospital at North Shore

Manhasset, New York, 11030, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

New York Presbyterian Hospital - Cornell Campus

New York, New York, 10021, United States

Location

Mount Sinai Medical Center, NY

New York, New York, 10029, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, 13217, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599-7295, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, 27104-4241, United States

Location

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, 38103, United States

Location

Vermont Cancer Center

Burlington, Vermont, 05401-3498, United States

Location

MBCCOP - Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Moncton Hospital

Moncton, New Brunswick, E1C 6ZB, Canada

Location

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, N6A 4L6, Canada

Location

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, L2R 5K3, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Cancer Care Ontario - Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2L-4M1, Canada

Location

McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• Friedenberg WR, Rue M, Blood EA, Dalton WS, Shustik C, Larson RA, Sonneveld P, Greipp PR. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer. 2006 Feb 15;106(4):830-8. doi: 10.1002/cncr.21666.

  PMID: 16419071 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Dexamethasone; Doxorubicin; valspodar; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: July 9, 2003
• Study Start: June 30, 1997
• Primary Completion: April 1, 2003
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

CA (8); US (32)