Clinical trial NCT01204502: Suicide Gene Therapy Trial
Official title: Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Haploidentical Stem Cell Transplantation
Keywords: Gene therapy
Haploidentical
Bone marrow transplant
Graft versus host disease
haploidentical stem cell transplantation
T-cell suicide gene therapy
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
First posted: 2010-09-17
Enrollment: 2
Sex: ALL
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
timeFrame: 12 months after final dose
Secondary outcomes:
measure: Incidence of GvHD
timeFrame: 12 months after final dose
measure: Patient survival
timeFrame: 12 months after final dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
Study officials:
References:
citation: 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.
citation: 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.