Suicide Gene Therapy Trial

Haploidentical Stem Cell Transplantation Clinical Trial

Official title:

Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01204502
• Other study ID #: 06MI04
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 16, 2010
• Last updated: September 17, 2013
• Start date: January 2011
• Est. completion date: January 2013

Study information

• Verified date: September 2013
• Source: Great Ormond Street Hospital for Children NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 16 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Haploidentical Stem Cell Transplantation

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Great Ormond Street Hospital for Children NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Patient survival	Patient survial is measured until 12 months after administration of the final dose of gene modified cells	12 months after final dose	No