RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be an effective treatment for myelodysplastic syndrome.

PURPOSE: Phase II trial to study the effectiveness of antithymocyte globulin plus cyclosporine 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 secondary myelodysplastic syndromes	Drug: anti-thymocyte globulin  Drug: cyclosporine  Procedure: biological response modifier therapy  Procedure: non-specific immune-modulator therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response in patients with myelodysplastic syndromes treated with anti-thymocyte globulin and cyclosporine.
• Determine the frequency and severity of toxic effects of this regimen in these patients.
• Assess the correlation between response to treatment and the in vitro assessment of T-lymphocyte subsets in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to myelodysplastic syndrome subclassification (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with excess blasts).

Patients receive induction therapy comprising anti-thymocyte globulin IV over 6-12 hours on days 1-4 and oral cyclosporine twice daily on days 5-94 followed by a taper until day 124. Patients who relapse after a response of at least 60 days may receive reinduction therapy comprising oral cyclosporine twice daily on days 1-90 followed by a taper until day 120. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 6 months, every 2 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 130 patients (53 with refractory anemia [RA], 33 with RA with ringed sideroblasts, and 44 with RA with excess blasts) will be accrued for this study within 14-22 months.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Morphologically confirmed myelodysplastic syndromes (MDS)
• Refractory anemia (RA)
• RA with ringed sideroblasts
• RA with excess blasts
• Low, intermediate-1, or intermediate-2 risk by International Prognostic Scoring System criteria
• MDS secondary to prior chemotherapy and/or radiotherapy for other malignant disorders allowed
• Must have received prior transfusions of at least 4 units of red blood cells for anemia within the past 60 days
• Must be concurrently registered on SWOG-S9910 and SWOG-9007
• Ineligible for or refused participation in SWOG-S9920 (HLA-identical sibling peripheral blood stem cell transplantation)

PATIENT CHARACTERISTICS: Age:

• 15 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• Prior cytokines (e.g., interferon or interleukin), colony-stimulating factors, or epoetin alfa allowed
• No prior bone marrow or stem cell transplantation
• No concurrent growth factors (including epoetin alfa) except filgrastim (G-CSF) or sargramostim (GM-CSF) for neutropenia

Chemotherapy:

• See Disease Characteristics
• No prior remission induction chemotherapy for MDS
• Prior hydroxyurea allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• Prior amifostine allowed
• No calcium-channel blockers (diltiazem, nicardipine, or verapamil), antifungals (fluconazole, itraconazole, or ketoconazole), antibiotics (clarithromycin or erythromycin), or other drugs (bromocriptine or danazol) that would increase cyclosporine concentrations for 48 hours before, during, and for 48 hours after cyclosporine
• No antibiotics (nafcillin or rifampin) or anticonvulsants (carbamazepine, phenobarbital, or phenytoin) that would decrease cyclosporine concentrations for 14 days before and during cyclosporine

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
      Veterans Affairs Medical Center - West Los Angeles, Los Angeles,  California,  90073,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813-2424,  United States
      Tripler Army Medical Center, Honolulu,  Hawaii,  96859-5000,  United States
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Iowa
      Genesis Medical Center, Davenport,  Iowa,  52804,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Medical Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      University of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Veterans Affairs Medical Center - Albany, Albany,  New York,  12208,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
Ohio
      Barrett Cancer Center, Cincinnati,  Ohio,  45267-0501,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97225,  United States
      Oregon Cancer Institute, Portland,  Oregon,  97239,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7845,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States
      Veterans Affairs Medical Center - Houston, Houston,  Texas,  77030,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78284,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Charles A. Schiffer, MD,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000068631; SWOG-S0020
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00016419
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08