Suicide Gene Therapy Trial

Study Overview
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Brief Summary
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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.

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

Conditions
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Haploidentical Stem Cell Transplantation

Intervention / Treatment
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* Biological: HSVTK retrovirally-transduced donor T lymphocytes


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSVTK retrovirally-transduced donor T lymphocytes<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 months after final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of GvHD | Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells | 12 months after final dose | 
| Patient survival | Patient survial is measured until 12 months after administration of the final dose of gene modified cells | 12 months after final dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy