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

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ClinicalTrials.gov Identifier: NCT00885833
Recruitment Status : Completed
First Posted : April 22, 2009
Last Update Posted : July 14, 2014
Sponsor:
Information provided by:
The Korean Society of Pediatric Hematology Oncology

Study Description
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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.

Condition or disease Intervention/treatment Phase
Wiskott-Aldrich Syndrome Drug: Fludarabine, Busulfan, Thymoglobulin Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome
Study Start Date : February 2007
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Fludarabine 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)


Outcome Measures
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Primary Outcome Measures :
  1. To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS. [ Time Frame: Feb. 2007 to Jan. 2012 ]
  2. To evaluate the incidence and severity of toxicity and treatment related mortality. [ Time Frame: Feb. 2007 to Jan. 2012 ]

Secondary Outcome Measures :
  1. To evaluate overall and event free survival rate. [ Time Frame: Feb. 2007 to Jan. 2012 ]
  2. To evaluate acute and chronic graft versus host disease (GVHD). [ Time Frame: Feb. 2007 to Jan. 2012 ]
  3. To evaluate immunologic recovery after HSCT. [ Time Frame: Feb. 2007 to Jan. 2012 ]

Eligibility Criteria
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Ages Eligible for Study:   1 Year to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00885833


Locations
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Korea, Republic of
Seoul National University Hospital
Seoul, Chongno-gu, Korea, Republic of, 110-744
Sponsors and Collaborators
The Korean Society of Pediatric Hematology Oncology
Investigators
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Principal Investigator: Hyo Seop Ahn, Ph. D The Korean Society of Pediatric Hematology Oncology
More Information
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Responsible Party: The Korean Society of Hematology, The Korean Society of Pediatric Hematology Oncology
ClinicalTrials.gov Identifier: NCT00885833    
Other Study ID Numbers: KSPHO-S0701
First Posted: April 22, 2009    Key Record Dates
Last Update Posted: July 14, 2014
Last Verified: July 2014
Keywords provided by The Korean Society of Pediatric Hematology Oncology:
Wiskott-Aldrich syndrome
HSCT
Additional relevant MeSH terms:
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Wiskott-Aldrich Syndrome
Syndrome
Disease
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphopenia
Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Primary Immunodeficiency Diseases
 Immunologic Deficiency Syndromes
Immune System Diseases
Fludarabine
Busulfan
Thymoglobulin
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists