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: Terminated
• Conditions: Haploidentical Stem Cell Transplantation
• Intervention / Treatment: Biological: HSVTK retrovirally-transduced donor T lymphocytes

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Great Ormond street Hospital for Children NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

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; dose 1 5x104 cells/kg; dose 2 5x105 cells/kg	Biological: 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; dose 1 5x104 cells/kg; dose 2 5x105 cells/kg

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)	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

Collaborators and Investigators

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

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: January 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: September 16, 2010
• First Submitted That Met QC Criteria: September 16, 2010
• First Posted (Estimate): September 17, 2010

Study Record Updates

• Last Update Posted (Estimate): September 18, 2013
• Last Update Submitted That Met QC Criteria: September 17, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Haploidentical; Graft versus host disease; Gene therapy; Bone marrow transplant; haploidentical stem cell transplantation; T-cell suicide gene therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide
• Other Study ID Numbers: 06MI04