Suicide Gene Therapy Trial

NHS Foundation Trust

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Haploidentical Stem Cell Transplantation

Treatments: Biological: HSVTK retrovirally-transduced donor T lymphocytes

Study type: Interventional

Funder types: Other

Identifiers

NCT01204502

06MI04

Details and patient eligibility

About

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.

Enrollment: 2 patients

Sex: All

Ages: Under 16 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

HSVTK retrovirally-transduced donor T lymphocytes

Experimental group

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

Treatment:

Biological: HSVTK retrovirally-transduced donor T lymphocytes