Thalidomide and Prednisone After Autologous Stem Cell Transplantation Multiple Myeloma

A Randomized Phase III Study Of Thalidomide And Prednisone As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients With Multiple Myeloma

RATIONALE: Thalidomide may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether combining thalidomide with prednisone and giving them after autologous stem cell transplantation may be effective in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying thalidomide and prednisone to see how well they work compared to observation in treating patients who have undergone stem cell transplantation for 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