Thalidomide and Prednisone After Autologous Stem Cell Transplantation Multiple Myeloma

OBJECTIVES:

• Compare overall survival of patients with multiple myeloma treated with thalidomide and prednisone as maintenance therapy vs observation alone after autologous stem cell transplantation.
• Compare progression-free survival of patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare toxic effects of these regimens in these patients.
• Compare the objective venous thromboembolism rate in symptomatic patients treated with these regimens.

OUTLINE: This is a randomized, non-blinded, multicenter study. Patients are stratified according to treatment center, age (under 60 vs 60 and over), and response to prior transplantation (complete vs incomplete). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral thalidomide daily and oral prednisone every other day for 4 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo observation.

For both arms, patients are assessed (including for quality of life) regularly throughout the treatment/observation period: at baseline, every 2 months for 6 months, every 3 months for up to 4 years, and then annually thereafter.

After the treatment/observation period, patients are followed annually..

PROJECTED ACCRUAL: A total of 324 patients will be accrued for this study within 3.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed multiple myeloma as evidenced by one of the following:

• Biopsy of an osteolytic lesion or soft tissue tumor composed of plasma cells
• Bone marrow aspirate and/or biopsy demonstrating at least 10% plasmacytosis
• Bone marrow less than 10% plasma cells with at least 1 bony lesion and meets the M-protein criteria as below
• Detectable serum M-component of IgG, IgA, IgD, or IgE at initial diagnosis OR
• Urinary excretion of light chain (Bence Jones) protein at least 1.0 gm/24 hrs if only light chain disease (urine M-protein) was present at initial diagnosis
• Previously treated with autologous stem cell transplantation after high-dose melphalan (200 mg/m^2) within the past 60-100 days

• Received transplantation within 1 year of the beginning of initial chemotherapy for multiple myeloma
• No evidence of disease progression

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• No prior hereditary hypercoaguable disorder
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and/or ALT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal

• Creatinine no greater than 3 times ULN

Cardiovascular

• No prior spontaneous deep vein thrombosis within the past 5 years

• Catheter-associated thrombus allowed
• No uncontrolled hypertension

Pulmonary

• No prior pulmonary embolism within the past 5 years

Other

• No other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or any cancer treated more than 5 years prior to study entry and presumed cured
• No prior gastric ulceration or bleeding within the past 5 years
• No prior documented lupus anti-coagulant or anti-phospholipid antibody
• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use 2 effective methods of contraception for 1 month prior, during, and 1 month after study participation
• Male patients must use effective barrier contraception during and for 1 month after study participation
• No avascular necrosis of the hips or shoulders
• No grade 2 or greater peripheral neuropathy causing symptomatic dysfunction (vincristine-induced sensory symptoms allowed)
• No diabetes with end-organ damage defined as:

• Documented diabetic neuropathy
• Retinal vascular proliferation requiring treatment
• Cardiovascular disease requiring active therapy
• Willing to complete quality of life questionnaires
• Employment does not prohibit the use of sedatives
• No other major medical illness or condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior double autologous or allogeneic hematopoietic stem cell transplantation
• No prior thalidomide

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent anti-cancer therapy
• No other concurrent investigational therapy