S0020 Immunosuppressive Therapy in Treating Patients With Myelodysplastic Syndrome

• ClinicalTrials.gov Identifier: NCT00016419
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: March 6, 2015
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Leukemia; Myelodysplastic Syndromes	Biological: anti-thymocyte globulin; Drug: cyclosporine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 130 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients With Myelodysplastic Syndrome (MDS)
• Study Start Date: August 2001
• Actual Primary Completion Date: July 2003
• Actual Study Completion Date: January 2007

Arms and Interventions

Intervention Details:

• Biological: anti-thymocyte globulin
  3.5 mg/kg/d IV over 12 hrs day 1
• Drug: cyclosporine
  3 mg/kg bid days 5-94 then taper to 0 at day 124 PO

Outcome Measures

Primary Outcome Measures :

1. total response [ Time Frame: after induction therapy is completed ]

Eligibility Criteria

• Ages Eligible for Study: 15 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

MBCCOP - Gulf Coast

Mobile, Alabama, United States, 36688

United States, Arizona

CCOP - Greater Phoenix

Phoenix, Arizona, United States, 85006-2726

Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)

Phoenix, Arizona, United States, 85012

Veterans Affairs Medical Center - Tucson

Tucson, Arizona, United States, 85723

Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Veterans Affairs Medical Center - Little Rock (McClellan)

Little Rock, Arkansas, United States, 72205

United States, California

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90033-0804

Veterans Affairs Medical Center - West Los Angeles

Los Angeles, California, United States, 90073

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States, 90095-1781

Veterans Affairs Outpatient Clinic - Martinez

Martinez, California, United States, 94553

CCOP - Bay Area Tumor Institute

Oakland, California, United States, 94609-3305

Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

University of California Davis Cancer Center

Sacramento, California, United States, 95817

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States, 95403

David Grant Medical Center

Travis Air Force Base, California, United States, 94535

United States, Colorado

University of Colorado Cancer Center

Denver, Colorado, United States, 80010

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States, 80220

United States, District of Columbia

MBCCOP - Howard University Cancer Center

Washington, District of Columbia, United States, 20060

United States, Georgia

CCOP - Atlanta Regional

Atlanta, Georgia, United States, 30342-1701

Dwight David Eisenhower Army Medical Center

Fort Gordon, Georgia, United States, 30905-5650

United States, Hawaii

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States, 96813-2424

Tripler Army Medical Center

Honolulu, Hawaii, United States, 96859-5000

United States, Illinois

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, United States, 60612-7323

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States, 60612

CCOP - Central Illinois

Decatur, Illinois, United States, 62526

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)

Hines, Illinois, United States, 60141

Loyola University Medical Center

Maywood, Illinois, United States, 60153-5500

United States, Iowa

Genesis Medical Center

Davenport, Iowa, United States, 52804

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160-7353

CCOP - Wichita

Wichita, Kansas, United States, 67214-3882

Veterans Affairs Medical Center - Wichita

Wichita, Kansas, United States, 67218

United States, Kentucky

Veterans Affairs Medical Center - Lexington

Lexington, Kentucky, United States, 40502-2236

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States, 40536-0084

United States, Louisiana

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States, 70112

Tulane University School of Medicine

New Orleans, Louisiana, United States, 70112

Louisiana State University Health Sciences Center - Shreveport

Shreveport, Louisiana, United States, 71130-3932

Veterans Affairs Medical Center - Shreveport

Shreveport, Louisiana, United States, 71130

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

Veterans Affairs Medical Center - Boston (Jamaica Plain)

Jamaica Plain, Massachusetts, United States, 02130

United States, Michigan

Veterans Affairs Medical Center - Ann Arbor

Ann Arbor, Michigan, United States, 48105

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States, 48106

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109-0912

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201-1379

Veterans Affairs Medical Center - Detroit

Detroit, Michigan, United States, 48201-1932

Henry Ford Hospital

Detroit, Michigan, United States, 48202

CCOP - Grand Rapids

Grand Rapids, Michigan, United States, 49503

CCOP - Beaumont

Royal Oak, Michigan, United States, 48073-6769

Providence Hospital - Southfield

Southfield, Michigan, United States, 48075-9975

United States, Mississippi

Veterans Affairs Medical Center - Biloxi

Biloxi, Mississippi, United States, 39531-2410

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216-4505

Veterans Affairs Medical Center - Jackson

Jackson, Mississippi, United States, 39216

Keesler Medical Center - Keesler AFB

Keesler AFB, Mississippi, United States, 39534-2576

United States, Missouri

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States, 64128

CCOP - Kansas City

Kansas City, Missouri, United States, 64131

St. Louis University Health Sciences Center

Saint Louis, Missouri, United States, 63110

CCOP - St. Louis-Cape Girardeau

Saint Louis, Missouri, United States, 63141

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States, 65807

United States, Montana

CCOP - Montana Cancer Consortium

Billings, Montana, United States, 59101

United States, New Mexico

Veterans Affairs Medical Center - Albuquerque

Albuquerque, New Mexico, United States, 87108-5138

MBCCOP - University of New Mexico HSC

Albuquerque, New Mexico, United States, 87131

United States, New York

Veterans Affairs Medical Center - Albany

Albany, New York, United States, 12208

Herbert Irving Comprehensive Cancer Center

New York, New York, United States, 10032

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, North Carolina

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States, 27104-4241

United States, Ohio

Veterans Affairs Medical Center - Cincinnati

Cincinnati, Ohio, United States, 45220-2288

Barrett Cancer Center

Cincinnati, Ohio, United States, 45267-0501

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44195-9001

CCOP - Columbus

Columbus, Ohio, United States, 43206

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States, 45428

CCOP - Dayton

Dayton, Ohio, United States, 45429

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

Veterans Affairs Medical Center - Oklahoma City

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States, 97207

CCOP - Columbia River Program

Portland, Oregon, United States, 97225

Oregon Cancer Institute

Portland, Oregon, United States, 97239

United States, South Carolina

Veterans Affairs Medical Center - Charleston

Charleston, South Carolina, United States, 29401-5799

Medical University of South Carolina

Charleston, South Carolina, United States, 29425-0721

CCOP - Greenville

Greenville, South Carolina, United States, 29615

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States, 29303

United States, Texas

Brooke Army Medical Center

Fort Sam Houston, Texas, United States, 78234-6200

University of Texas Medical Branch

Galveston, Texas, United States, 77555-0565

Veterans Affairs Medical Center - Houston

Houston, Texas, United States, 77030

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78284-7845

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States, 78284

Veterans Affairs Medical Center - Temple

Temple, Texas, United States, 76504

CCOP - Scott and White Hospital

Temple, Texas, United States, 76508

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112-5550

Veterans Affairs Medical Center - Salt Lake City

Salt Lake City, Utah, United States, 84148

United States, Washington

CCOP - Virginia Mason Research Center

Seattle, Washington, United States, 98101

Veterans Affairs Medical Center - Seattle

Seattle, Washington, United States, 98108

CCOP - Northwest

Tacoma, Washington, United States, 98405-0986

Madigan Army Medical Center

Tacoma, Washington, United States, 98431-5000

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

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

More Information

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00016419
• Other Study ID Numbers: S0020; S0020 ( Other Identifier: SWOG ); U10CA032102 ( U.S. NIH Grant/Contract )
• First Posted: January 27, 2003
• Last Update Posted: March 6, 2015
• Last Verified: March 2015

Keywords provided by Southwest Oncology Group:

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:

Preleukemia; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Neoplasms; Cyclosporine; Cyclosporins; Antilymphocyte Serum; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors