Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome
Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome
RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be
 effective treatment for myelodysplastic syndrome. It is not yet known whether
 immunosuppressive therapy is more effective than supportive care in treating myelodysplastic
 syndrome.

 PURPOSE: Randomized phase II trial to compare the effectiveness of antithymocyte globulin
 with that of supportive care in treating patients who have 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