Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome

April 24, 2017 updated by: St. Jude Children's Research Hospital

Haploidentical Hematopoietic Stem Cell Transplantation for Pediatric Patients With Wiskott-Aldrich Syndrome: A Pilot Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Secondary Objectives in this trial include the following:

  • To estimate the survival of study recipients at one year after infusion of the T- and B-lymphocyte depleted stem cell graft.
  • To assess if the study treatment enables the recipient to generate normal donor-derived B-cell numbers and endogenous IgM, IgG, and IgA production, resulting in a reduction/elimination of the need for intravenous immunoglobulin infusions.
  • To determine if the study treatment results in the ability of the research participant to generate normal donor-derived T cell response and natural killer (NK) cell numbers and function.
  • To describe the incidence of Epstein-Barr virus-lymphoproliferative disease (EBV-LPD) in these transplant recipients.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 1
Procedure: Hematopoietic stem cell transplantation
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.
Other Names:
  • Allogeneic stem cell transplant
  • Mismatched family member donor transplant
  • Haploidentical stem cell transplant
  • T and B cell depletion
Device: Miltenyi CliniMACS selection system
This system depletes the hematopoietic stem cell graft of T and B lymphocytes.
Drug: Fludarabine, Melphalan, Thiotepa
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: March 2010
March 2010

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

April 26, 2017

Last Update Submitted That Met QC Criteria

April 24, 2017

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WASHAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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