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Combination Chemotherapy With or Without Interferon Alfa in Treating Patients With Previously Untreated Multiple Myeloma
This study is ongoing, but not recruiting participants.
First Received: November 1, 1999   Last Updated: March 25, 2009   History of Changes
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002556
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether combination chemotherapy plus interferon alfa is more effective than combination chemotherapy alone in treating patients with multiple myeloma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without interferon alfa in treating patients who have previously untreated stage I, stage II, or stage III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: filgrastim
Biological: recombinant interferon alfa
Drug: carmustine
Drug: cyclophosphamide
Drug: melphalan
Drug: prednisone
Drug: vincristine sulfate
Phase III

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
Drug Information available for: Cyclophosphamide Prednisone Vincristine Interferon alfa-2a Filgrastim Interferon alfa-n1 Melphalan Carmustine Vincristine sulfate Interferons
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: THE TREATMENT OF MULTIPLE MYELOMA UTILIZING VBMCP CHEMOTHERAPY ALTERNATING WITH HIGH-DOSE CYCLOPHOSPHAMIDE AND ALPHA 2B-INTERFERON VERSUS VBMCP: A PHASE III STUDY FOR PREVIOUSLY UNTREATED MULTIPLE MYELOMA

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 289
Study Start Date: April 1994
Detailed Description:

OBJECTIVES:

  • Compare the response rate, time to response, duration of response, and survival in patients with previously untreated multiple myeloma treated with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alone vs VBMCP alternating first with high-dose cyclophosphamide and then with interferon alfa in patients with previously untreated multiple myeloma.
  • Compare the toxicity of these regimens in these patients.
  • Determine whether ancillary laboratory studies on companion protocol E-3A93 predict response and survival on this protocol.

OUTLINE: This is a randomized study. Patients are stratified according to creatinine (less than 2.0 vs 2.0 mg/dL or greater), performance status (0-1 vs 2-4), plasma cell labeling index (2% or more vs less than 2% vs approved unknown/not interpretable), and beta-2 microglobulin (4 micrograms/dL or greater vs less than 4 micrograms/dL vs approved unknown/not interpretable).

  • Induction: Patients receive vincristine IV, carmustine IV, and cyclophosphamide (CTX) IV on day 1; oral melphalan on days 1-4; and oral prednisone on days 1-7 (VBMCP). Treatment continues every 5 weeks for 2 courses.
  • Consolidation: Patients are then randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive VBMCP as in induction. Courses repeat every 5 weeks.
    • Arm II: Courses 1-3 each last 5 weeks, while subsequent courses each last 3 weeks. During courses 1 and 3, patients receive oral prednisone and high-dose CTX IV on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Patients receive VBMCP during course 2 and all subsequent even-numbered courses. Patients receive interferon alfa (IFN-A) SC three times a week for 10 doses during course 5 and all subsequent odd-numbered courses. The last dose for each course of IFN-A is administered concurrently with day 1 of course 6 and subsequent courses of VBMCP. Patients continue to receive alternating courses of VBMCP and IFN-A.

After documentation of plateau, patients receive 2 additional courses of VBMCP (arm I) or 2 additional courses of VBMCP alternating with 2 courses of IFN-A (arm II) in the absence of disease progression. Treatment for arms I and II continues for 1-2 years in the absence of a plateau state plus 2 additional courses of VBMCP (arm I) or 2 courses each of VBMCP and IFN-A (arm II); disease progression; or unacceptable toxicity. Patients undergo observation beginning after completion of the 2 post-plateau courses and continuing in the absence of disease progression. Patients with disease progression after 3 months on observation receive reinduction comprising the consolidation regimen to which they were originally randomized. Reinduction continues in the absence of disease progression.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 289 patients will be accrued for this study within approximately 8 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of previously untreated, stage I-III multiple myeloma confirmed by:

    • Bone marrow plasmacytosis with at least 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytoma
    • At least 1 of the following:

      • M-protein in serum or urine
      • Osteolytic lesions on radiograph (generalized osteoporosis qualifies only if bone marrow aspirate contains at least 20% plasma cells)
  • Measurable disease

    • Serum M-protein at least 1.0 g/dL by serum protein electrophoresis
    • Urine M-protein (light chain) excretion greater than 200 mg/24 hours by urine protein electrophoresis
    • Biopsy-proven, measurable plasmacytoma(s) of soft tissue
    • Bone marrow plasmacytosis of at least 20%
  • No smoldering multiple myeloma
  • No nonsecretory myeloma
  • No localized plasmacytomas
  • No monoclonal gammopathy of undetermined significance
  • No primary systemic amyloidosis
  • No cord compression or CNS complication unless controlled by appropriate therapy
  • Concurrent registration on the ancillary laboratory protocol E-3A93 required except for participants from South African institutions

PATIENT CHARACTERISTICS:

Age:

  • 18 and over
  • Patients age 70 and over eligible if considered able to tolerate study therapy

Performance status:

  • Under age 70: Known EGOG performance status
  • Age 70 and over: ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 50,000/mm^3
  • No thrombophlebitis within the past 6 months

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • SGOT no greater than 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2.5 times ULN

Renal:

  • Creatinine no greater than 5.0 mg/dL
  • No renal disease
  • No hyperuricemia unless controlled by appropriate therapy

Cardiovascular:

  • No myocardial infarction within the past 6 months
  • No hypertension requiring treatment other than diuretics and/or beta blockers, angiotensin-converting enzyme inhibitors, or calcium channel blockers
  • Blood pressure greater than 140/90 mm Hg must be treated and maintained below 170/100 mm Hg on antihypertensives
  • No significant arrhythmia within the past 3 months, i.e.:

    • Sustained atrial or ventricular arrhythmia requiring antiarrhythmic drugs
    • Documented multifocal premature ventricular contractions requiring therapy
    • Ongoing requirement for antiarrhythmia drugs except digoxin to control the ventricular rate of atrial fibrillation that has been chronic for more than 1 year
  • Ejection fraction normal by echocardiogram or MUGA scan if history of congestive heart failure or myocardial infarction
  • No angina requiring nitrates or beta blockers

Pulmonary:

  • No pulmonary emboli within the past 6 months

Other:

  • No AIDS
  • No concurrent reversible condition (e.g., infection, hyperviscosity syndrome) unless controlled by appropriate therapy
  • No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Concurrent epoetin alfa allowed for control of anemia

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Concurrent corticosteroids for hypercalcemia allowed

Radiotherapy:

  • No prior radiotherapy to more than 15% of bone marrow
  • Concurrent radiotherapy allowed if delay of systemic therapy would pose undue risk to patient

Surgery:

  • More than 5 years since prior surgery for other cancer

Other:

  • See Cardiovascular
  • Concurrent bisphosphonates or other agents for hypercalcemia allowed
  • No concurrent anticoagulants
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002556

Locations
United States, Illinois
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Robert A. Kyle, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000063435, E-5A93
Study First Received: November 1, 1999
Last Updated: March 25, 2009
ClinicalTrials.gov Identifier: NCT00002556     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Study placed in the following topic categories:
Anti-Inflammatory Agents
Prednisone
Melphalan
Interferon Type I, Recombinant
Immunologic Factors
Blood Protein Disorders
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Alkylating Agents
Interferon-alpha
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hematologic Diseases
Blood Coagulation Disorders
Interferons
Carmustine
Vascular Diseases
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Antiviral Agents
Angiogenesis Inhibitors
Multiple Myeloma
Tubulin Modulators

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Anti-Infective Agents
Prednisone
Interferon Type I, Recombinant
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Interferon-alpha
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Growth Substances
Mitosis Modulators
Interferons
Carmustine

ClinicalTrials.gov processed this record on May 07, 2009