Suicide Gene Therapy Trial

NCT01204502 | Terminated Phase 1

• 1 other identifier: 06MI04
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Incidence of GvHD

  12 months after final dose

• Patient survival

  12 months after final dose

Study Arms (1)

HSVTK retrovirally-transduced donor T lymphocytes

EXPERIMENTAL

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

Interventions

HSVTK retrovirally-transduced donor T lymphocytes BIOLOGICAL

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

HSVTK retrovirally-transduced donor T lymphocytes

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead

Study Sites (1)

Great Ormond Street Hospital for Children NHS Trust

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 15638716 BACKGROUND

• 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.

  PMID: 24204746 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: January 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: September 18, 2013

Record last verified: 2013-09

Locations

GB (1)