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

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ClinicalTrials.gov Identifier: NCT01231841
Recruitment Status : Completed
First Posted : November 1, 2010
Results First Posted : March 9, 2012
Last Update Posted : February 22, 2018
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE October 29, 2010
First Posted Date  ICMJE November 1, 2010
Results First Submitted Date  ICMJE January 31, 2012
Results First Posted Date  ICMJE March 9, 2012
Last Update Posted Date February 22, 2018
Study Start Date  ICMJE March 2005
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2010)
Response rate of r-ATG and CsA in the first line setting [ Time Frame: At 3 months ]
Change History Complete list of historical versions of study NCT01231841 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2010)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia
Official Title  ICMJE 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)
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Aplastic Anemia
Intervention  ICMJE
  • Drug: cyclosporine
    Given orally
    Other Names:
    • 27-400
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Biological: anti-thymocyte globulin
    Given IV
    Other Names:
    • ATG
    • ATGAM
    • lymphocyte immune globulin
    • Thymoglobulin
Study Arms  ICMJE 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
Interventions:
  • Drug: cyclosporine
  • Biological: anti-thymocyte globulin
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 25, 2011)
20
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2010)
38
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01231841
Other Study ID Numbers  ICMJE CCF7922
NCI-2010-01365 ( Other Identifier: NCI/CTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jaroslaw Maciejewski Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account The Cleveland Clinic
Verification Date January 2018

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