Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial Assessing The Safety And Efficacy Of Thalidomide (THALOMID) For The Treatment Of Anemia In Red Blood Cell Transfusion-Dependent Patients With Myelodysplastic Syndromes

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: thalidomide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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