Suicide Gene Therapy Trial

This study has been terminated.
(Changes in the clinical practice)
Sponsor:
Information provided by:
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01204502
First received: September 16, 2010
Last updated: September 17, 2013
Last verified: September 2013
  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:


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


Enrollment: 2
Study Start Date: January 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204502

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Trust
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: September 17, 2013
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 August 28, 2014