Dexamethasone With or Without Thalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

A Randomized Phase III Trial Of Thalidomide (NSC # 66847) Plus Dexamethasone Versus Dexamethasone In Newly Diagnosed Multiple Myeloma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining dexamethasone and thalidomide may kill more cancer cells. It is not yet known whether dexamethasone is more effective with or without thalidomide in treating multiple myeloma.

PURPOSE: Randomized phase III trial to determine the effectiveness of dexamethasone with or without thalidomide in treating patients who have multiple myeloma.

OBJECTIVES:

• Compare the response rate of patients with newly diagnosed multiple myeloma treated with dexamethasone with or without thalidomide.
• Compare the toxicity of these regimens in these patients.
• Assess the effect of thalidomide on bone marrow microvessel density and angiogenesis grade and on the expression of vascular endothelial growth factor and basic fibroblast growth factor in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral thalidomide once daily on days 1-28 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients also receive either pamidronate IV over 2-4 hours or zoledronate IV over 15 minutes on day 1 for bone strengthening.
• Arm II: Patients receive dexamethasone and pamidronate or zoledronate as in arm I.

Treatment in both arms repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional courses after the fourth course at the physician's discretion.

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

PROJECTED ACCRUAL: A total of 194 patients (97 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Newly diagnosed symptomatic multiple myeloma confirmed by the following:

  • Bone marrow plasmacytosis with at least 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytosis
  • Monoclonal protein (M protein) at least 1.0 g/dL on serum protein electrophoresis or at least 200 mg of monoclonal light chain on a 24-hour urine protein electrophoresis

• No smoldering myeloma or monoclonal gammopathy of undetermined significance

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 50,000/mm^3
• Hemoglobin greater than 7 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT and AST no greater than 2.5 times upper limit of normal

Renal:

• Creatinine less than 3 mg/dL

Cardiovascular:

• No prior or concurrent deep venous thrombosis

Other:

• Prior malignancy allowed provided the following criteria are met:

  • Received prior treatment with curative intent
  • Free of disease for the time period appropriate for cure of the specific cancer

• No grade 2 or greater peripheral neuropathy due to other medical conditions

• No active infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 1 highly effective method and 1 additional method of contraception for 1 month before, during, and for 4 weeks after study for women and effective barrier contraception for men during and for 4 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy for multiple myeloma
• No other concurrent biologic therapy for multiple myeloma

Chemotherapy:

• No prior chemotherapy for multiple myeloma
• No other concurrent chemotherapy for multiple myeloma

Endocrine therapy:

• More than 6 months since prior systemic dexamethasone or glucocorticoids
• No concurrent corticosteroids

Radiotherapy:

• At least 4 weeks since prior palliative, localized radiotherapy
• Concurrent palliative, localized radiotherapy allowed at the physician's discretion

Surgery:

• Not specified

Other:

• No prior systemic therapy for multiple myeloma, except bisphosphonates
• No concurrent anticoagulant therapy for deep vein thrombosis
• No concurrent barbiturates or alcohol (thalidomide arm)