Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia
This study has been completed.
Sponsor:
The Cleveland Clinic
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
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Purpose
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: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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 ] [ 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.
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) ] [ 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.
| 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:
Other: flow cytometry
Correlative studies
Biological: anti-thymocyte globulin
Given IV
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 12 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01231841
Locations
| United States, Ohio | |
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | |
| Cleveland, Ohio, United States, 44195 | |
Sponsors and Collaborators
The Cleveland Clinic
Investigators
| Principal Investigator: | Jaroslaw Maciejewski | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center |
More Information
No publications provided by The Cleveland Clinic
Additional 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 |
| Study First Received: | October 29, 2010 |
| Results First Received: | January 31, 2012 |
| Last Updated: | March 25, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Anemia Anemia, Aplastic Hematologic Diseases Bone Marrow Diseases Antilymphocyte Serum Cyclosporins Cyclosporine Immunoglobulins Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 16, 2013