S0020 Immunosuppressive Therapy in Treating Patients With Myelodysplastic Syndrome

A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients With Myelodysplastic Syndrome (MDS)

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Leukemia
• Intervention / Treatment: Biological: anti-thymocyte globulin; Drug: cyclosporine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
total response	after induction therapy is completed

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Charles A. Schiffer, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): July 1, 2003
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: refractory anemia; refractory anemia with ringed sideroblasts; refractory anemia with excess blasts; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood myelodysplastic syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: S0020 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)