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Suicide Gene Therapy Trial

Primary Purpose

Haploidentical Stem Cell Transplantation

Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
HSVTK retrovirally-transduced donor T lymphocytes
Sponsored by
Great Ormond Street Hospital for Children NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Haploidentical Stem Cell Transplantation focused on measuring Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy

Eligibility Criteria

undefined - 16 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Great Ormond Street Hospital for Children NHS Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HSVTK retrovirally-transduced donor T lymphocytes

Arm Description

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

Outcomes

Primary Outcome Measures

T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells

Secondary Outcome Measures

Incidence of GvHD
Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells
Patient survival
Patient survial is measured until 12 months after administration of the final dose of gene modified cells

Full Information

First Posted
September 16, 2010
Last Updated
September 17, 2013
Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT01204502
Brief Title
Suicide Gene Therapy Trial
Official Title
Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Why Stopped
Changes in the clinical practice
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Haploidentical Stem Cell Transplantation
Keywords
Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HSVTK retrovirally-transduced donor T lymphocytes
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
HSVTK retrovirally-transduced donor T lymphocytes
Intervention Description
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
Primary Outcome Measure Information:
Title
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
Description
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
Time Frame
12 months after final dose
Secondary Outcome Measure Information:
Title
Incidence of GvHD
Description
Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells
Time Frame
12 months after final dose
Title
Patient survival
Description
Patient survial is measured until 12 months after administration of the final dose of gene modified cells
Time Frame
12 months after final dose

10. Eligibility

Sex
All
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with primary immunodeficiencies, haematological malignancies or metabolic disorders at GOSH (children of both sexes, aged 0 to 16 years) undergoing haploidentical transplant Both patient and donor must give informed consent in writing. The donor must be willing, able and available for donation of T cells by collection of whole blood or leukapheresis. The patient should be free of serious intercurrent illness. Exclusion Criteria: Donor unfit or unavailable Donor positive for Hepatitis B or C, or HTLV-1, or HIV Patient receiving Ganciclovir, Aciclovir, Cidofovir a result of active CMV, adenovirus, varicella zoster or herpes simplex infection infection GVHD ≥ grade II before infusion of gene modified T cells Serious intercurrent illness
Facility Information:
Facility Name
Great Ormond Street Hospital for Children NHS Trust
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
15638716
Citation
Qasim W, Gaspar HB, Thrasher AJ. T cell suicide gene therapy to aid haematopoietic stem cell transplantation. Curr Gene Ther. 2005 Feb;5(1):121-32. doi: 10.2174/1566523052997497.
Results Reference
background
PubMed Identifier
24204746
Citation
Zhan H, Gilmour K, Chan L, Farzaneh F, McNicol AM, Xu JH, Adams S, Fehse B, Veys P, Thrasher A, Gaspar H, Qasim W. Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene. PLoS One. 2013 Oct 21;8(10):e77106. doi: 10.1371/journal.pone.0077106. eCollection 2013.
Results Reference
derived

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Suicide Gene Therapy Trial

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