An Open Label, Prospective, Stratified, Randomized, Controlled, Multi-Center, Phase IIB Study of the Impact of Thymoglobulin Therapy on Transfusion Needs of Patients With Early Myelodysplastic Syndrome (MDS)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed early myelodysplastic syndrome (MDS) with
less than 10% bone marrow blasts

- Refractory anemia (RA)

- RA with excess blasts (RAEB)

- Hypocellular myelodysplasia

- Low or intermediate-1 prognostic risk

- Transfusion-dependent

- Need for 2 or more units of red blood cells or platelets per month for 2 or more
months prior to study OR

- History of prior transfusions and 2 consecutive (at least 21 days apart)
hemoglobin levels less than 8.0 g/dL or platelet counts less than 20,000/mm^3
during the past 2 months

- Hemoglobin no greater than 12.0 g/dL after prior transfusion

- No myelosclerosis occupying more than 30% of bone marrow space

- No RA with ringed sideroblasts, RAEB in transformation, or chronic myelomonocytic
leukemia

- No therapy-related MDS

- No history of immune-related hematologic disorder (e.g., idiopathic thrombocytopenic
purpura)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 3 months

Hematopoietic:

- See Disease Characteristics

- No other causes of cytopenia unrelated to MDS (e.g., gastrointestinal blood loss)

- Iron present on marrow examination OR

- Transferrin saturation at least 20% and ferritin at least 50 ng/mL

Hepatic:

- Bilirubin no greater than 2 mg/dL OR

- SGOT/SGPT no greater than 2 times normal

- No active or chronic hepatitis B or C

Renal:

- Creatinine no greater than 2 mg/dL

Cardiovascular:

- No symptomatic cardiac disease

- No congestive heart failure (even if medically controlled)

- No myocardial infarction within the past 6 months

Pulmonary:

- No severe pulmonary disease

- If history of pulmonary insufficiency, must have pO_2 at least 90 mm/Hg on room air
or pCO_2 no greater than 40 mm/Hg

Other:

- No history of unresolved B12 or folate deficiency since diagnosis of MDS

- No untreated acute or chronic infection (afebrile for 7 days without antibiotics
prior to study)

- No active or chronic HIV

- No concurrent cytomegalovirus infection

- No other malignancy within the past 2 years except adequately treated localized
squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

- No concurrent drug or alcohol abuse

- No significant medical or psychosocial problems

- No known allergy to rabbit protein

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 8 weeks since prior biologic agents, colony-stimulating factors, or epoetin
alfa for MDS

- At least 8 weeks since other prior investigational biologic agents

- No prior or concurrent bone marrow transplantation

- No concurrent epoetin alfa

- No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) for
neutropenic fevers

- No other concurrent biologic agents

Chemotherapy:

- At least 8 weeks since prior cytotoxic drugs for MDS

- Concurrent chemotherapy for clinical indications of disease progression or leukemic
transformation allowed

Endocrine therapy:

- At least 8 weeks since prior androgenic hormonal therapy for MDS

- At least 8 weeks since prior danazol for MDS

Radiotherapy:

- No prior radiotherapy

Surgery:

- No prior organ transplantation

Other:

- At least 8 weeks since prior investigational drugs

- At least 8 weeks since prior immunosuppressive drugs or other drugs for MDS

- No concurrent immunosuppressive therapy

- No other concurrent experimental drugs