Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome

NCT00160355 | Completed Phase 1

• 1 other identifier: WASHAP
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Wiskott - Aldrich syndrome (WAS) is a rare disorder curable only through allogeneic hematopoietic stem cell transplantation. A mismatched family member is an option when no human leukocyte antigen (HLA-immune system type) matched related or matched unrelated donor is available. This study will evaluate a novel therapeutic strategy for patients with WAS who undergo haploidentical transplantation using a parental donor. To reduce the risk of transplant-related toxicities, participants will receive a reduced intensity chemotherapy and antibody regimen (conditioning treatment). Participants will then receive an infusion of donor stem cells depleted of certain white blood cells called T- and B-lymphocytes. The stem cell depletion processing will be done through the use of the investigational CliniMACS device. A certain number of T-lymphocytes will be added back to the processed stem cell graft prior to infusion into the recipient. The primary objective of this study is to determine the safety of haploidentical transplantation in WAS patients using this specified conditioning regimen and engineered graft. Safety will be defined in terms of engraftment (meaning how well the graft grows and functions after infusion) and regimen-related toxicity within the first 100 days after transplant.

Conditions

Wiskott-Aldrich Syndrome

Keywords

Wiskott-Aldrich Syndrome; Immunodeficiency; Haploidentical transplantation

Outcome Measures

Primary Outcomes (1)

• To determine safety in regards to engraftment and toxicity within 100 days post-haploidentical T- and B-cell depleted hematopoietic stem cell transplantation for patients with Wiskott-Aldrich syndrome who received a reduced intensity conditioning

  March 2010

Study Arms (1)

1

OTHER

Procedure: Hematopoietic stem cell transplantation; Device: Miltenyi CliniMACS selection system; Drug: Fludarabine, Melphalan, Thiotepa

Interventions

Hematopoietic stem cell transplantation PROCEDURE

To determine the safety in regards to engraftment and toxicity within 100 days of infusing a haploidentical T- and B-cell depleted hematopoietic stem cell graft into patients with Wiskott-Aldrich syndrome who have received a reduced intensity conditioning regimen.

Also known as: Haploidentical stem cell transplant, Allogeneic stem cell transplant, Mismatched family member donor transplant, T and B cell depletion

1

Miltenyi CliniMACS selection system DEVICE

This system depletes the hematopoietic stem cell graft of T and B lymphocytes.

1

Fludarabine, Melphalan, Thiotepa DRUG

Participants will receive a reduced intensity conditioning regimen consisting of Fludarabine, Melphalan, Thiotepa, and OKT3 prior to receipt of the haploidentical stem cell graft. Rituximab will be given in an effort to prevent PTLPD. In addition to T-cell depletion of the donor product, cyclosporine will be given for GVHD prophylaxis.

1

Eligibility Criteria

• Age: Up to 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Genotypical diagnosis of Wiskott-Aldrich Syndrome.
• Less than 18 years of age at time of transplant.
• Must meet two of the eight following clinical criteria:
• Eczema that is refractory to standard therapy.
• Thrombocytopenia as defined by a platelet count \< 50,000/mm3.
• Significant risk for or presence of opportunistic infection.
• Autoimmune disease.
• Malignancy or pre-malignant condition.
• Family history as defined as a family member with WAS who died before 10 years of age.
• Does not have a suitable, available 6/6 HLA-matched sibling donor available for donation.
• Does not have a suitable, available 10/10 HLA-allele matched unrelated donor identified through the National Marrow Donor Program (NMDP).

You may not qualify if:

• If any of the following clinical indicators are met within 45 days prior to transplant, the research participant will not be eligible for the study:
• Symptomatic cardiac disease or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction \< 30%).
• Creatinine clearance or Tc 99 less than or equal 40ml/min/1.73 m2.
• SGPT greater than or equal 500 U/L.
• Karnofsky or Lansky Performance Score of \< 50.
• Pulmonary function tests: FVC \< 50% of predicted value if age appropriate to perform the testing adequately or an O2 saturation less than or equal to 92% on room air at rest.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Wiskott-Aldrich Syndrome; Immunologic Deficiency Syndromes

Interventions

Hematopoietic Stem Cell Transplantation; fludarabine; Melphalan; Thiotepa

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kimberly Kasow, DO

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: May 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: February 1, 2009
• Last Updated: April 26, 2017

Record last verified: 2009-02

Locations

US (1)