Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)

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Brief Title

Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)

Official Title

Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome

Brief Summary

      Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immune-deficiency syndrome and
      hematopoietic stem cell transplantation (HSCT) has become a curative modality. But the
      transplant with the conventional conditioning resulted in high incidence of treatment related
      toxicities and non-myeloablative conditioning resulted in high incidence of engraftment
      failure. Recently, fludarabine based reduced toxicity myeloablative conditioning regimen was
      developed for adult myeloid malignancies with promising result of good engraftment and low
      treatment related toxicities. To increase the engraftment potential without serious
      complication, reduced toxicity myeloablative conditioning regimen composed of fludarabine,
      busulfan, and thymoglobulin is designed for Wiskott-Aldrich syndrome.
    

Detailed Description

      Wiskott-Aldrich syndrome (WAS) is an rare X-linked congenital immune-deficiency syndrome
      characterized by the triad of recurrent infection, eczema and thrombocytopenia with small
      size of platelet (Puck JM, 2006). Clinical studies revealed high rate of autoimmune disorder
      and malignancy in WAS (Ochs HD, 2006). The identification of the molecular defect in 1994
      (Derry JM, 1994) has broadened the clinical spectrum of the syndrome to include chronic or
      intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS and X-lined
      neutropenia caused by an arrest of myelopoiesis (Ochs HD, 2006).

      The incidence of WAS in Korea was very low and only 6 patients diagnosed between 2001 and
      2005 (Kim JG, 2006).

      Conventional treatments for WAS such as prophylactic antibiotics and immune globin for
      infection and platelet transfusion for bleeding were not so successful (Thrasher AJ, 2000).
      Bone marrow transplantation (BMT) from an HLA-matched related donor is an effective treatment
      (Filipovich AH, 2001) and patients without appropriate related donor could receive
      alternative stem cell source such as matched unrelated donor or cord blood. But the
      transplant with the alternative donor needed more intensive conditioning to overcome the
      hematologic and immunologic barrier with increased treatment related toxicity. Further
      progress depends in particular on the development of alternative preparative conditioning
      regimens which allow stable engraftment of donor precursor cells with minimal systemic toxic
      side effects (Friedrich W, 2004).

      Recently, we reported successful unrelated bone marrow transplantation in a boy with WAS with
      reduced toxicity myeloablative conditioning regimen to increase the engraftment potential
      without serious complication (Kang, 2008), and extended to multicenter phase I/II pilot study
      with this reduced toxicity myeloablative conditioning regimen in the HSCT for WAS.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS.

Secondary Outcome

 To evaluate overall and event free survival rate.

Condition

Wiskott-Aldrich Syndrome

Intervention

Fludarabine, Busulfan, Thymoglobulin

Study Arms / Comparison Groups

 Fludarabine
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

5

Start Date

February 2007

Completion Date

March 2012

Primary Completion Date

March 2012

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of Wiskott-Aldrich syndrome with gene analysis.

          2. Indicated for hematopoietic stem cell transplantation.

          3. Age: no limitation.

          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%, ejection fraction > 45%.

               -  Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of
                  normal.

               -  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 hematopoietic stem cell donor is available.

          8. Patients (or one of parents if patients age < 19) should sign informed consent.

        Exclusion Criteria:

          1. Pregnant or nursing women.

          2. Malignant (except acute myeloid leukemia) or nonmalignant illness that is uncontrolled
             or whose control may be jeopardized by complications of study therapy.

          3. Psychiatric disorder that would preclude compliance.
      

Gender

All

Ages

1 Year - 25 Years

Accepts Healthy Volunteers

No

Contacts

Hyo Seop Ahn, Ph. D, , 

Location Countries

Korea, Republic of

Location Countries

Korea, Republic of

Administrative Informations


NCT ID

NCT00885833

Organization ID

KSPHO-S0701



Study Sponsor

The Korean Society of Pediatric Hematology Oncology


Study Sponsor

Hyo Seop Ahn, Ph. D, Principal Investigator, The Korean Society of Pediatric Hematology Oncology


Verification Date

July 2014