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Suicide Gene Therapy Trial

This study is currently recruiting participants.
Verified March 2012 by Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor:
Information provided by:
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01204502
First received: September 16, 2010
Last updated: March 1, 2012
Last verified: March 2012
History of Changes
  Purpose

Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft-versus-host disease (GVHD).

To safeguard against GVHD, the investigators propose modifying T cells to encode a 'switch' so that they can be eliminated if problems arise.

Children receiving half-matched (haploidentical) transplants from a parent are most likely to benefit from this strategy. At present these patients receive blood stem cells from a parent, but the T cells are removed because the risk of serious GVHD is unacceptable. This means that they are much more likely to suffer from life threatening infections or experience a relapse of leukaemia. The investigators want to use gene therapy to produce "safe" T cells which can be used to strengthen the transplant and prevent these serious complications.


Condition Intervention Phase
Haploidentical Stem Cell Transplantation
 Biological: HSVTK retrovirally-transduced donor T lymphocytes
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Suicide
U.S. FDA Resources

Further study details as provided by Great Ormond Street Hospital for Children NHS Foundation Trust:

Primary Outcome Measures:
  • T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3) [ Time Frame: 12 months after final dose ] [ Designated as safety issue: No ]
    T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells


Secondary Outcome Measures:
  • Incidence of GvHD [ Time Frame: 12 months after final dose ] [ Designated as safety issue: No ]
    Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells

  • Patient survival [ Time Frame: 12 months after final dose ] [ Designated as safety issue: No ]
    Patient survial is measured until 12 months after administration of the final dose of gene modified cells


Estimated Enrollment: 10
Study Start Date: January 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HSVTK retrovirally-transduced donor T lymphocytes

HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD

  • dose 1 5x104 cells/kg
  • dose 2 5x105 cells/kg
 Biological: HSVTK retrovirally-transduced donor T lymphocytes

HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD

  • dose 1 5x104 cells/kg
  • dose 2 5x105 cells/kg

  Eligibility

Ages Eligible for Study:   up to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with primary immunodeficiencies, haematological malignancies or metabolic disorders at GOSH (children of both sexes, aged 0 to 16 years) undergoing haploidentical transplant
  2. Both patient and donor must give informed consent in writing.
  3. The donor must be willing, able and available for donation of T cells by collection of whole blood or leukapheresis.
  4. The patient should be free of serious intercurrent illness.

Exclusion Criteria:

  1. Donor unfit or unavailable
  2. Donor positive for Hepatitis B or C, or HTLV-1, or HIV
  3. Patient receiving Ganciclovir, Aciclovir, Cidofovir a result of active CMV, adenovirus, varicella zoster or herpes simplex infection infection
  4. GVHD ≥ grade II before infusion of gene modified T cells
  5. Serious intercurrent illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01204502

Contacts
Contact: Anne-Marie McNicol, Dr 0207 905 2292 anne-marie.mcnicol@ich.ucl.ac.uk

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Trust Recruiting
London, United Kingdom, WC1N 3JH
Principal Investigator: Waseem Qasim, Dr            
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

Publications:

Responsible Party: Biren Patel, Great Ormond Street Hospital for Children NHS Trust
ClinicalTrials.gov Identifier: NCT01204502     History of Changes
Other Study ID Numbers: 06MI04
Study First Received: September 16, 2010
Last Updated: March 1, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Great Ormond Street Hospital for Children NHS Foundation Trust:
Gene therapy
Haploidentical
Bone marrow transplant
 Graft versus host disease
haploidentical stem cell transplantation
T-cell suicide gene therapy

Additional relevant MeSH terms:
Suicide
Self-Injurious Behavior
Behavioral Symptoms

ClinicalTrials.gov processed this record on May 16, 2013