Thalidomide and Epoetin Alfa in Treating Anemia in Patients With Myelodysplastic Syndrome

OBJECTIVES:

• Determine whether the combination of epoetin alfa and thalidomide improves the anemia and/or decreases the need for red cell transfusion in patients with low- or intermediate-risk myelodysplastic syndromes.
• Determine whether this regimen improves the bone marrow morphology and cytogenetics, alters the natural history of the disease, and reduces the frequency of leukemic transformation in these patients.
• Evaluate whether this regimen improves pathophysiologic parameters (e.g., apoptosis, tumor necrosis factor-alpha concentration, microvessel density, vascular endothelial growth factor, and cytotoxic T lymphocytes) in the bone marrow of these patients.
• Determine the safety of this regimen in these patients.

OUTLINE: Patients receive epoetin alfa subcutaneously (SC) once weekly for 8 weeks. After 8 weeks, patients unresponsive to epoetin alfa alone receive oral thalidomide once daily in addition to epoetin alfa SC once weekly for a maximum of 24 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study within 2 years..

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes

• Newly diagnosed OR
• Prior treatment was unsuccessful, including treatment with chemotherapy
• International prognostic scoring system score no greater than 1.5
• Hemoglobin no greater than 10 g/dL (untransfused) AND/OR
• Received at least 3 units of packed red blood cells for symptomatic anemia within the past 6 weeks

PATIENT CHARACTERISTICS:

Age

• Over 21

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• See Disease Characteristics
• No prior bleeding disorder

Hepatic

• Bilirubin less than 2 mg/dL
• ALT/AST less than 2 times upper limit of normal

Renal

• Creatinine less than 1.5 mg/dL

Cardiovascular

• No prior clinically significant heart disease
• No uncontrolled hypertension
• No recent thromboembolic disease (e.g., deep vein thrombosis)

• Prior thromboembolic events allowed provided event occurred at least 6 weeks prior to study and patient is on anticoagulants and is clinically stable

Pulmonary

• No unstable pulmonary disease
• No recent pulmonary embolism
• No active pulmonary infection

Neurologic

• No pre-existing peripheral neuropathy greater than grade 2
• No sustained neurologic deficit
• No epilepsy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods (including 1 highly effective method) of contraception for at least 4 weeks before, during, and for at least 4 weeks after study completion
• No active infection
• No concurrent illness that would obscure toxicity or dangerously alter drug metabolism
• No other serious concurrent medical illness
• No uncontrolled diabetes mellitus
• No other malignant disease (except non-melanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission and off therapy for that disease for more than 1 year
• No known hypersensitivity to mammalian cell-derived products or human albumin

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 4-6 weeks since prior therapy