RATIONALE: Antithymocyte globulin and cyclosporine may improve blood counts in patients with myelodysplastic syndrome. It is not yet known whether antithymocyte globulin and cyclosporine are more effective than standard therapy for myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of antithymocyte globulin and cyclosporine with that of standard therapy in treating patients who have myelodysplastic syndrome.

Condition	Treatment or Intervention	Phase
Refractory Anemia refractory anemia with ringed sideroblasts refractory anemia with excess blasts de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes	Drug: anti-thymocyte globulin  Drug: cyclosporine  Procedure: biological response modifier therapy  Procedure: non-specific immune-modulator therapy	Phase III

OBJECTIVES:

• Compare the efficacy and toxicity of antithymocyte globulin and cyclosporine versus best supportive care in patients with transfusion dependent low or intermediate risk myelodysplastic syndrome.
• Determine whether immunosuppression improves hematopoiesis and reduces transfusion requirements of these patients.
• Determine whether immunosuppression accelerates leukemic transformation and influences survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center and risk group.

Patients are randomized to 1 of 2 treatment arms:

• Arm I: Patients receive antithymocyte globulin IV over 3 hours on days 1-5 and oral cyclosporine twice daily on days 1-180.
• Arm II: Patients receive standard supportive care without antithymocyte globulin and cyclosporine. Patients are followed at 1, 3, and 6 months, then every 6 months for 1.5 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 84 patients (42 per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of low or intermediate risk myelodysplastic syndrome (MDS) of less than 2 years duration with any of the following:
• Hypoplasia
• Refractory anemia
• Refractory anemia with sideroblasts
• Refractory anemia with excess of blasts (RAEB) with no greater than 10% blast cells in bone marrow
• RAEB with 10-20% blast count, and patient refuses intensive chemotherapy on high risk MDS protocol (EORTC 06961) and is not eligible for bone marrow transplantation
• Transfusion dependence, defined by any of the following:
• Packed red blood cell transfusions greater than 2 units per month for a period of at least 2 months
• Untransfused hemoglobin level no greater than 8 g/dL
• Platelet transfusions greater than 1 unit per 2 weeks for a period of greater than 1 month
• Untransfused platelet count no greater than 20,000/mm^3
• No chronic myelomonocytic leukemia
• No refractory anemia with excess blasts in transformation
• Not scheduled for a bone marrow transplantation

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• ECOG/SAKK 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• No active chronic hepatitis B or C

Renal:

• Creatinine no greater than 2.5 times ULN

Cardiovascular:

• No history of heart failure
• No clinically relevant cardiac arrhythmia

Other:

• No other prior malignancy except nonmelanomatous skin cancer or adequately treated carcinoma in situ of the cervix
• No history of allergy to horse proteins, anaphylactic reactions to animal proteins, or serum sickness
• Not pregnant
• Fertile patients must use effective contraception
• HIV negative
• No active uncontrolled infection

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Switzerland
      Universitätsspital-Basel, Basel,  CH-4031,  Switzerland; Recruiting

Study chairs or principal investigators

A. Tichelli, MD,  Study Chair,  Universitätsspital-Basel   

Study ID Numbers:  CDR0000067455; SWS-SAKK-33/99; EU-99029
Record last reviewed:  May 2001
Record first received:  January 21, 2000
ClinicalTrials.gov Identifier:  NCT00004208
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29