Suicide Gene Therapy Trial

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust (Other)

Overall Status

Terminated

CT.gov ID

NCT01204502

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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