Haploidentical Stem Cell Transplantation
Conditions
Keywords
Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy
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.
Interventions
BIOLOGICALHSVTK 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
Sponsors
Great Ormond Street Hospital for Children NHS Foundation Trust
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 16 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom
Outcome results
None listed