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

NCT ID: NCT00885833

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2012-03-31

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.

Conditions

Wiskott-Aldrich Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine

Group Type: EXPERIMENTAL

Fludarabine, Busulfan, Thymoglobulin

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Korean Society of Pediatric Hematology Oncology

NETWORK

Sponsor Role: lead

Responsible Party

The Korean Society of Pediatric Hematology Oncology

Principal Investigators

Hyo Seop Ahn, Ph. D

Role: PRINCIPAL_INVESTIGATOR

The Korean Society of Pediatric Hematology Oncology

Locations

Seoul National University Hospital

Seoul, Chongno-gu, South Korea

Countries

South Korea

Other Identifiers

KSPHO-S0701

Identifier Type: -

Identifier Source: org_study_id