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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.
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01231841
First received: October 29, 2010
Last updated: March 25, 2013
Last verified: March 2013

October 29, 2010
March 25, 2013
March 2005
December 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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.
Response rate of r-ATG and CsA in the first line setting [ Time Frame: At 3 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01231841 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
  • Reduction of VB Repertoire Associated With r-ATG/CsA Combination [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
    We will perform molecular analysis of the TCR repertoire to identify "marker" immunodominant clone specimens using VB typing.
Same as current
Not Provided
Not Provided
 
Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia
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)

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Aplastic Anemia
  • 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
    • ATGAM
    • lymphocyte immune globulin
    • Thymoglobulin
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
Interventions:
  • Drug: cyclosporine
  • Other: flow cytometry
  • Biological: anti-thymocyte globulin
Afable MG 2nd, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP. Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia. Haematologica. 2011 Sep;96(9):1269-75. doi: 10.3324/haematol.2011.042622. Epub 2011 May 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01231841
CCF7922, NCI-2010-01365
Yes
The Cleveland Clinic
The Cleveland Clinic
Not Provided
Principal Investigator: Jaroslaw Maciejewski Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
The Cleveland Clinic
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP