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Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: November 1, 2010
Last Update Posted: April 1, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
The Cleveland Clinic
RATIONALE: Immunosuppressive therapies, such as anti-thymocyte globulin and cyclosporine, may improve bone marrow function and increase blood cell counts. PURPOSE: This phase II trial is studying how well giving anti-thymocyte globulin together with cyclosporine as first-line therapy works in treating patients with severe aplastic anemia.

Condition Intervention Phase
Aplastic Anemia Drug: cyclosporine Other: flow cytometry Biological: anti-thymocyte globulin Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol for Prospective Phase II Study of Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) and Cyclosporine (CsA) as a First Line Immunosuppressive (IS) Therapy for Severe Aplastic Anemia (sAA)

Resource links provided by NLM:

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Patients Treated With Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) and Cyclosporine (CsA) Achieving at Least a Partial Remission (PR) at 6 Months [ Time Frame: At 6 months ]
    Patients will be classified as responders if they have transfusion independence and meet two of the following three criteria: ANC greater than 500/mm3; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3. Transfusion independence is defined as no need for transfusions for one month prior to response assessment.

Secondary Outcome Measures:
  • Comparison of the Level of IS as Assessed by Immuknow Assay in Responders and Non-responders [ Time Frame: Every 2 weeks for 3 months beginning on day 1 of therapy and then monthly (for a total of 6 months) ]
  • Reduction of VB Repertoire Associated With r-ATG/CsA Combination [ Time Frame: Every 4 weeks ]
    We will perform molecular analysis of the TCR repertoire to identify "marker" immunodominant clone specimens using VB typing.

Enrollment: 20
Study Start Date: March 2005
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rATG
Patients receive anti-thymocyte globulin IV daily over 4-24 hours on days 1-5. Beginning on day 6, patients receive oral cyclosporine twice daily for 6 months followed by a taper. Treatment continues in the absence of disease progression or unacceptable toxicity
Drug: cyclosporine
Given orally
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Other: flow cytometry
Correlative studies
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
  • lymphocyte immune globulin
  • Thymoglobulin

Detailed Description:
PRIMARY OBJECTIVES: To determine the response rate of r-ATG and CsA in the first line setting. SECONDARY OBJECTIVES: To determine the level of IS as assessed by Immuknow assay in responders and compare it to non-responders. OUTLINE:Patients receive anti-thymocyte globulin IV over 4-24 hours daily on days 1-5. Beginning on day 6, patients receive oral cyclosporine twice daily for 6 months followed by a taper. Treatment continues in the absence of disease progression or unacceptable toxicity.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All patients with sAA as defined by Camitta who are candidates for IS therapy; these criteria include bone marrow cellularity < 25% or 25-50% with < 30% of hematopoietic cells; it should also have two of the following three parameters: peripheral blood neutrophils < 0.5 x 10^9/L, platelets < 20 x 10^9/L and reticulocytes < 60 x 10^9/L in anemic patients
  • If cytogenetic testing has been done, it should show normal karyotype or be not informative
  • Patients should be either unwilling or otherwise ineligible (age, comorbidities, lack of donor) for bone marrow transplantation as a therapeutic modality
  • Not previously treated with ATG for sAA
  • Patients must have ECOG performance status of 0, 1, or 2
  • Vitamin B12 and folic acid deficiency must be ruled out by measurement of serum levels
  • Patients must have had a bone marrow biopsy examination in the three months prior to enrolling in the study
  • Must be able to provide informed consent
  • Systemic and other hematologic causes of pancytopenia, based on clinical presentation, must have been ruled out

Exclusion Criteria:

  • Patients with clinically evident congestive heart failure, serious cardiac arrhythmias; symptoms of coronary artery disease must be cleared by cardiology prior to therapy
  • Patients who have had chemotherapy, radiotherapy, or immunotherapy or other investigational drug use within 3 weeks prior to study entry
  • Pregnant women
  • All females of childbearing potential must have a blood test or urine study within two weeks prior to induction registration to rule out pregnancy
  • Women of childbearing potential are strongly advised to use an accepted and effective method of contraception
  • Patients who have medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231841

United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Principal Investigator: Jaroslaw Maciejewski Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01231841     History of Changes
Other Study ID Numbers: CCF7922
NCI-2010-01365 ( Other Identifier: NCI/CTRP )
First Submitted: October 29, 2010
First Posted: November 1, 2010
Results First Submitted: January 31, 2012
Results First Posted: March 9, 2012
Last Update Posted: April 1, 2013
Last Verified: March 2013

Additional relevant MeSH terms:
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
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