thalidomide in treating anemia in patients with myelodysplastic syndrome

Conditions: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Summary: rationale: thalidomide may be an effective treatment for anemia caused by myelodysplastic syndrome. purpose: randomized phase ii trial to study the effectiveness of thalidomide in treating anemia in patients who have myelodysplastic syndrome.

objectives: * determine the efficacy of thalidomide for the treatment of anemia in patients with myelodysplastic syndromes. * determine whether this drug reduces the frequency of leukemia transformation and decreases bone marrow blast percentage in these patients. * determine the effect of this drug on neutrophil and platelet production and the number of episodes of febrile neutropenia in these patients. * determine the safety of this drug in these patients. outline: this is a randomized, double-blind, placebo-controlled, multicenter study. patients are stratified according to international prognostic scoring system score (low and intermediate-1 vs intermediate-2 and high) and transfusion dependence (yes vs no). patients are randomized to one of two treatment arms. * arm i: patients receive oral thalidomide once daily on weeks 1-24. * arm ii: patients receive oral placebo once daily on weeks 1-24. in both arms, patients who have not progressed to leukemia after 24 weeks of therapy may receive open-label thalidomide for an additional 24 weeks in the absence of disease progression or unacceptable toxicity. patients are followed at 4 weeks. projected accrual: a total of 220 patients (110 per treatment arm) will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of myelodysplastic syndromes (mds) of at least 12 weeks duration * refractory anemia (ra) * ra with ringed sideroblasts * ra with excess blasts * chronic myelomonocytic * no therapy-related mds * no myelosclerosis or myelofibrosis occupying more than 30% of marrow space (or assessed as grade 3+ or greater) * no transformation to acute myeloid leukemia * no more than 20% blasts in bone marrow * no more than 5% blasts in peripheral blood * patients with an erythropoietin level 100 mu/ml or less must have failed epoetin alfa treatment (i.e., at least 30,000 units of epoetin alfa weekly for at least 6 weeks) * transfusion-dependent (received at least 2 units of packed rbcs or whole blood within the past 8 weeks) or * transfusion-independent (no packed rbc or whole blood transfusions within the past 8 weeks with 2 hemoglobin levels (at least 7 days apart) less than 11 g/dl) * no iron deficiency (e.g., absent bone marrow iron store) * if marrow aspirate is not evaluable, transferrin saturation must be at least 20% and ferritin at least 50 ng/ml * no uncorrected b12 or folate deficiency * no other contributing causes of anemia (e.g., autoimmune or hereditary hemolytic disorders or gastrointestinal blood loss) patient characteristics: age: * 18 and over performance status: * ecog 0-2 or * zubrod 0-2 life expectancy: * at least 6 months hematopoietic: * see disease characteristics * absolute neutrophil count at least 500/mm\^3 hepatic: * bilirubin no greater than 2.0 mg/dl * ast and alt less than 2 times upper limit of normal (uln) * hepatitis b surface antigen negative * hepatitis c negative renal: * creatinine no greater than 1.5 times uln cardiovascular: * no uncontrolled hypertension * no clinically significant, symptomatic, unstable cardiovascular disease unrelated to mds pulmonary: * no clinically significant, symptomatic, unstable pulmonary disease unrelated to mds neurologic: * no clinically significant, symptomatic, unstable neurologic disease unrelated to mds * no history of epilepsy * no sustained neurologic deficit (e.g., stroke) * no grade 2 or greater peripheral neuropathy other: * not pregnant or nursing * negative pregnancy test * fertile patients must use at least 1 highly effective and 1 additional effective method of contraception for 4 weeks prior to, during, and for 4 weeks after study participation * hiv negative * no clinically significant, symptomatic, unstable endocrine, gastrointestinal, or genitourinary disease unrelated to mds * no other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no life-threatening or active infection requiring parenteral antibiotics * no other serious concurrent illness prior concurrent therapy: biologic therapy: * see disease characteristics * more than 7 days since prior hematopoietic growth factors (e.g., epoetin alfa, filgrastim (g-csf), sargramostim (gm-csf), or interleukin-3) * no prior thalidomide * no prior agents intended to inhibit vascular endothelial growth factor or tumor necrosis factor alfa (e.g., etanercept or infliximab) * no concurrent epoetin alfa chemotherapy: * no concurrent chemotherapy that may be active against mds endocrine therapy: * more than 30 days since prior androgens * no requirement for ongoing therapy with systemic corticosteroids radiotherapy: * not specified surgery: * not specified other: * more than 30 days since prior treatment for mds except rbc transfusion or epoetin alfa * more than 30 days since prior participation in another experimental clinical trial * more than 30 days since prior experimental drugs * no other concurrent investigational agents or treatments

Keywords: refractory anemia refractory anemia with ringed sideroblasts refractory anemia with excess blasts de novo myelodysplastic syndromes chronic myelomonocytic leukemia previously treated myelodysplastic syndromes myelodysplastic/myeloproliferative neoplasm, unclassifiable atypical chronic myeloid leukemia, bcr-abl1 negative