Suicide Gene Therapy Trial
Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
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London, United Kingdom, WC1N 3JH
- Great Ormond Street Hospital for Children NHS Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
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HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
Time Frame: 12 months after final dose
|
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
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12 months after final dose
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of GvHD
Time Frame: 12 months after final dose
|
Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells
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12 months after final dose
|
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Patient survival
Time Frame: 12 months after final dose
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Patient survial is measured until 12 months after administration of the final dose of gene modified cells
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12 months after final dose
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Collaborators and Investigators
Publications and helpful links
General Publications
- Qasim W, Gaspar HB, Thrasher AJ. T cell suicide gene therapy to aid haematopoietic stem cell transplantation. Curr Gene Ther. 2005 Feb;5(1):121-32. doi: 10.2174/1566523052997497.
- Zhan H, Gilmour K, Chan L, Farzaneh F, McNicol AM, Xu JH, Adams S, Fehse B, Veys P, Thrasher A, Gaspar H, Qasim W. Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene. PLoS One. 2013 Oct 21;8(10):e77106. doi: 10.1371/journal.pone.0077106. eCollection 2013.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 06MI04
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