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

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2010

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.

Interventions

  • Drug: cyclosporine
    • Given orally
  • Biological: anti-thymocyte globulin
    • Given IV

Arms, Groups and Cohorts

  • Experimental: rATG + Cyclosporine
    • 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

Clinical Trial Outcome Measures

Primary 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 12 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • The Cleveland Clinic
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jaroslaw Maciejewski, Principal Investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

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