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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: anti-thymocyte globulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|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 excess blasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes