Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)

March 23, 2012 updated by: The Korean Society of Pediatric Hematology Oncology

Reduced Toxicity Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia

Anti-thymocyte globulin (ATG) has been used in severe aplastic anemia as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing graft versus host disease (GVHD) and rejection of organ transplants. As the fludarabine based conditioning regimens without total body irradiation have been reported to be promising for transplantation from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated donor transplantation. Our previous phase II study of fludarabine, cyclophosphamide plus thymoglobulin conditioning resulted in good engraftment (100%) and survival rate (74%). But grade III/IV toxicities occurred in 25% of patients and all events were treatment related mortalities. As cyclophosphamide is more toxic agent than fludarabine, we plan a new phase II study re; 'reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated donor transplantation in severe aplastic anemia' by reducing dosage of cyclophosphamide and increasing dosage of fludarabine.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

33

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

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Hyo Seop Ahn, M.D, Ph.D
          • Phone Number: 82 2 2072 3625
          • Email: hsahn@snu.ac.kr

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

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion.

    • Peripheral blood

      1. Neutrophils < 0.5 x 109/l
      2. Platelets < 20 x 109/l
      3. Corrected reticulocytes < 1%

    • Bone marrow

      1. Severe hypocellularity (< 25%)
      2. Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells
  2. No prior hematopoietic stem cell transplantation.
  3. Age: no limits.
  4. Performance status: ECOG 0-2.

  5. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases:

    • Heart: a shortening fraction > 30% and ejection fraction > 45%.
    • Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper
    • Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.
  6. Patients must lack any active viral infections or active fungal infection.
  7. Appropriate donor is available: Matched in 6/6 of A, B, DR loci.
  8. Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria:

  1. Pregnant or nursing women.
  2. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
  3. Psychiatric disorder that would preclude compliance.
  4. Congenital aplastic anemia including Fanconi anemia.
  5. Manipulated bone marrow.

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
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fludarabine
Drug: Cyclophosphamide, Fludarabine, Thymoglobulin

cyclophosphamide (60 mg/kg once daily i.v. on days -8, -7)

fludarabine (40 mg/m2 once daily i.v. on days -6, -5, -4, -3, -2)

thymoglobulin (2.5 mg/kg once daily i.v. on days -4, -3, -2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate engraftment potential of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.
Time Frame: From Nov. 2008 to Oct. 2012
From Nov. 2008 to Oct. 2012

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA.
Time Frame: From Nov. 2008 to Oct. 2012
From Nov. 2008 to Oct. 2012
To evaluate overall and EFS rate after UBMT/PBSCT.
Time Frame: From Nov. 2008 to Oct. 2012
From Nov. 2008 to Oct. 2012
To evaluate GVHD and immunologic recovery after UBMT/PBSCT.
Time Frame: From Nov. 2008 to Oct. 2012
From Nov. 2008 to Oct. 2012

Collaborators and Investigators

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

Sponsor

The Korean Society of Pediatric Hematology Oncology

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

November 1, 2008

Primary Completion (Anticipated)

October 1, 2012

Study Completion (Anticipated)

October 1, 2012

Study Registration Dates

First Submitted

April 15, 2009

First Submitted That Met QC Criteria

April 15, 2009

First Posted (Estimate)

April 16, 2009

Study Record Updates

Last Update Posted (Estimate)

March 26, 2012

Last Update Submitted That Met QC Criteria

March 23, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KSPHO-SCT 0802

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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