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

This study has been completed.
Sponsor:
Information provided by:
The Korean Society of Pediatric Hematology Oncology
ClinicalTrials.gov Identifier:
NCT00885833
First received: April 21, 2009
Last updated: July 11, 2014
Last verified: July 2014

April 21, 2009
July 11, 2014
February 2007
March 2012   (final data collection date for primary outcome measure)
  • To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS. [ Time Frame: Feb. 2007 to Jan. 2012 ] [ Designated as safety issue: No ]
  • To evaluate the incidence and severity of toxicity and treatment related mortality. [ Time Frame: Feb. 2007 to Jan. 2012 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00885833 on ClinicalTrials.gov Archive Site
  • To evaluate overall and event free survival rate. [ Time Frame: Feb. 2007 to Jan. 2012 ] [ Designated as safety issue: No ]
  • To evaluate acute and chronic graft versus host disease (GVHD). [ Time Frame: Feb. 2007 to Jan. 2012 ] [ Designated as safety issue: No ]
  • To evaluate immunologic recovery after HSCT. [ Time Frame: Feb. 2007 to Jan. 2012 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)
Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Wiskott-Aldrich Syndrome
Drug: Fludarabine, Busulfan, Thymoglobulin
fludarabine (40 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4 & -3) busulfan (0.8 mg/kg every 6 hours i.v. on days -6, -5, -4, & -3) thymoglobulin (2.5 mg/kg once daily i.v. on days -8, -7, -6 for cord blood and on days -4, -3, -2 for bone marrow or mobilized peripheral blood)
Experimental: Fludarabine
Intervention: Drug: Fludarabine, Busulfan, Thymoglobulin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
March 2012
March 2012   (final data collection date for primary outcome measure)

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.
Both
1 Year to 25 Years
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00885833
KSPHO-S0701
No
The Korean Society of Hematology, The Korean Society of Pediatric Hematology Oncology
The Korean Society of Pediatric Hematology Oncology
Not Provided
Principal Investigator: Hyo Seop Ahn, Ph. D The Korean Society of Pediatric Hematology Oncology
The Korean Society of Pediatric Hematology Oncology
July 2014

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