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

Inclusion 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