Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome

OBJECTIVES:

• Compare the clinical response rate of patients with early myelodysplastic syndrome treated with rabbit anti-thymocyte globulin vs standard supportive care.
• Evaluate the safety of anti-thymocyte globulin in these patients.
• Compare the time to and duration of clinical response, rates of partial response and therapy failure, and rate of disease progression in patients treated with these regimens.
• Compare the ECOG performance score, number of transfusions and/or growth factor use, and maximum time between transfusions in patients treated with these regimens.
• Compare the infection risk, use of medical resources, and quality of clinical response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to myelodysplastic syndrome (MDS) subtype (refractory anemia (RA) vs RA with excess blasts or hypocellular MDS). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rabbit anti-thymocyte globulin (ATG) IV over at least 8-12 hours on days 1-4.
• Arm II: Patients receive standard supportive therapy for 6 months. At the end of 6 months, patients may receive ATG as in arm I.

Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 72 patients (48 in arm I and 24 in arm II) will be accrued within a minimum of 6 months.

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