Combination Chemotherapy With or Without Cyclophosphamide and Prednisone in Treating Older Patients With Multiple Myeloma - Full Text View

Sponsored by:	Medical Research Council
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002653

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective in treating older patients with multiple myeloma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without cyclophosphamide and prednisone in treating older patients with multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: carmustine Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: melphalan Drug: prednisone Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	VIIITH MYELOMATOSIS TRIAL: A RANDOMISED TRIAL OF TREATMENT FOR INDUCING FIRST PLATEAU PHASE ABCM VS 3 COURSES OF ABCM FOLLOWED BY ORAL WEEKLY CYCLOPHOSPHAMIDE

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma Radiation Therapy

Drug Information available for: Cyclophosphamide Prednisone Doxorubicin Doxorubicin hydrochloride Myocet Melphalan Carmustine

U.S. FDA Resources

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

Estimated Enrollment:	1000
Study Start Date:	September 1993

Detailed Description:

OBJECTIVES:

Compare the efficacy of doxorubicin, carmustine, cyclophosphamide, and melphalan (ABCM) with or without oral cyclophosphamide and prednisone as induction for the first plateau phase in elderly patients with previously untreated multiple myeloma.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center.

Patients receive doxorubicin IV followed immediately by carmustine IV over 1-2 hours on day 1 and oral melphalan (L-PAM) and oral cyclophosphamide (CTX) on days 22-25 (ABCM). Treatment continues every 6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients whose blood counts recover within 6 weeks after beginning L-PAM and CTX during course 3 are randomized to 1 of 2 treatment arms. Patients whose blood counts fail to recover within 6 weeks after beginning L-PAM and CTX during course 3 are assigned to arm II.

Arm I: Patients continue ABCM for a maximum of 12 courses in the absence of a plateau phase after completion of at least 4 courses, disease progression, or unacceptable toxicity.
Arm II: Patients receive oral cyclophosphamide once weekly and oral prednisone every other day. Treatment continues every 6 weeks in the absence of a plateau phase after completion of 3 courses of ABCM plus a minimum of 8 weeks on arm II or less than 3 courses of ABCM plus 6 months on arm II, disease progression, or unacceptable toxicity. Patients on both arms with bone pain or failure to respond to chemotherapy may undergo minimal radiotherapy.

Patients achieving plateau phase may enter the MRC trial of interferon alfa-2b.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within approximately 5 years.

Eligibility

Ages Eligible for Study:	65 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma, defined by at least 2 of the following conditions:
- Neoplastic cell infiltrate and/or microplasmacytomas by bone marrow sections or smears
  - Plasma cell infiltrates greater than 20% of marrow nucleated cells or, if less than 20%, objective evidence of monoclonality of the plasma cells required
- Paraprotein in blood or urine
- Definite lytic bone lesions (not osteoporosis)
Nonsecretory disease allowed in the presence of 1 of the following conditions:
- Microplasmacytomas
- Monoclonal plasmacytosis with immunoglobulin light-chain expression in cytoplasm
No equivocal myelomatosis, defined by the following criteria:
- Minimal or no symptoms attributable to myelomatosis
- Pretransfusion hemoglobin greater than 10 g/dL
- Post-hydration creatinine less than 1.47 mg/dL
- No osteolytic lesions except minimal lesions that do not threaten pathological fracture and are not associated with pain
- Plasma cells less than 30% of marrow nucleated cells and marrow showing normal hematopoietic activity
- Serum beta-2 microglobulin less than 4 mg/L
- Less than 1 g of free light-chain excretion per 1 g of creatinine
- No objective factors indicating progressive myelomatosis

PATIENT CHARACTERISTICS:

Age:

65 to 74
If under 65, higher priority is given to protocol MRC-LEUK-MYEL-VII unless entry into this study would be more appropriate

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics
Neutrophil count at least 1,300/mm^3
Platelet count at least 75,000/mm^3

Hepatic:

Not specified

Renal:

See Disease Characteristics

Other:

Ability to tolerate fluid intake of at least 3 L/day beginning at least 2 days before study entry
Afebrile and free of infection
No contraindication to therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Prior or concurrent prednisolone at 30 mg/m2/day or less (or equivalent doses of other corticosteroids) for relief of fluid-unresponsive hypercalcemia allowed

Radiotherapy:

Prior or concurrent minimal local radiotherapy to relieve persistent bone pain or cord compression allowed

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002653

Locations

United Kingdom, England
MRC Myelomatosis Trials Office
Birmingham, England, United Kingdom, B15 2SZ

Sponsors and Collaborators

Medical Research Council

Investigators

Study Chair:

M. T. Drayson, MD

MRC Myelomatosis Trials Office

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000064187, MRC-LEUK-MYEL-VIII, EU-94031
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00002653 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
Immunologic Factors
Blood Protein Disorders
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Hormones
Anti-Bacterial Agents
Hemorrhagic Disorders
Alkylating Agents

Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hematologic Diseases
Blood Coagulation Disorders
Carmustine
Vascular Diseases
Immunosuppressive Agents
Glucocorticoids
Doxorubicin
Multiple Myeloma
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Antirheumatic Agents
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Blood Protein Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Cyclophosphamide
Antibiotics, Antineoplastic
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Therapeutic Uses

Cardiovascular Diseases
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Carmustine
Vascular Diseases
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Multiple Myeloma
Neoplasms

ClinicalTrials.gov processed this record on September 01, 2009