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.

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

Further Study Details: 

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.

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

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
• 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

District of Columbia
      Washington Cancer Institute, Washington,  District of Columbia,  20010,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Illinois
      Rush Cancer Institute, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Blood and Marrow Transplant, Beech Grove,  Indiana,  46107,  United States
Iowa
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Louisiana
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Missouri
      Saint Louis University Cancer Center, Saint Louis,  Missouri,  63110-2539,  United States
      Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
      University of Missouri Kansas City School of Medicine, Kansas City,  Missouri,  64111,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      James P. Wilmot Cancer Center, Rochester,  New York,  14642,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Texas
      Texas Oncology P.A., Dallas,  Texas,  75230-2503,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226-3596,  United States
Canada, Alberta
      Foothills Hospital, Calgary,  Alberta,  T2N 2T9,  Canada
Canada, British Columbia
      Department of Medicine, Vancouver,  British Columbia,  V5Z 4E3,  Canada
Canada, Ontario
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada

Study chairs or principal investigators

Elizabeth C. Squiers, MD,  Study Chair,  Sangstat Medical Corporation   

Study ID Numbers:  CDR0000068709; SMC-101-1020; RUSH-MDS-2000-04
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017550
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08