Suicide Gene Therapy Trial

Phase 1

Terminated

• Conditions: Haploidentical Stem Cell Transplantation
• Interventions: Biological: HSVTK retrovirally-transduced donor T lymphocytes

• Registration Number: NCT01204502
• Lead Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-09-16
• Study First Submitted QC: 2010-09-16
• Study First Posted: 2010-09-17
• Study Start: 2011-01
• Primary Completion: 2013-01
• Study Completion: 2013-01
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-17
• Last Update Posted: 2013-09-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSVTK retrovirally-transduced donor T lymphocytes	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Great Ormond Street Hospital for Children NHS Trust; 🇬🇧 London, United Kingdom