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

May 25, 2023 updated by: The Cleveland Clinic

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymphocyte immune globulin
Drug: cyclosporine
Given orally
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
Every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Cleveland Clinic

Investigators

  • Principal Investigator: Jaroslaw Maciejewski, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

October 29, 2010

First Submitted That Met QC Criteria

October 29, 2010

First Posted (Estimated)

November 1, 2010

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

May 25, 2023

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCF7922
  • NCI-2010-01365 (Other Identifier: NCI/CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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