Present: Professor Norman Nevin (Chair), Professor Terry Hamblin, Dr Adrian Lepper, Professor Nick Lemoine, Dr Caroline Benjamin, Dr Peter Harris, Dr Michael Waterhouse, Dr Richard Ashcroft, Professor Andrew Lever, Professor Alex Markham, Mrs Fiona Sandford, Mr Michael Harrison, Rev Dr Lee Rayfield, Professor David Harrison, & Professor Martin Gore.

Secretariat: Dr Jayne Spink, Mr Daniel Gooch

Observers: Dr Sharon Longhurst (MHRA), Dr Paul Logan (HSE).

Apologies: Dr Monika Preuss (Secretariat)

Item 1: Welcome

The Chair welcomed the Committee to its 54th meeting, and congratulated Dr Harris, Mrs Beirne, and Prof Lemoine on their reappointments by DH Ministers to serve a further term on GTAC.

Item 2: Minutes of the 53rd meeting of GTAC

The minutes were agreed as an accurate and true record of the 53rd meeting.

Item 3: Matters Arising & Chairman's Actions

A number of letters were sent out, and received, concerning correspondence arising from the last meeting, none of which gave rise to significant discussion.

Item 4: New Protocol: 108 An open-labelled, international, multicenter, dose escalating, phase I/II study of SPC2996, an LNA antisense molecule against Bcl-2, in patients with relapsed or refractory Chronic Lymphocytic Leukaemia

The product called SPC2996 is a 16-base oligonucleotide designed to bind to the messenger RNA of a gene called Bcl2 and in doing so prevents the RNA being "read" by the cells machinery. In this way the aim is to stop production of the Bcl2 protein which can prevent cancer cells from undergoing programmed cell death (apoptosis). The antisense will be injected intravenously into patients with Chronic Lymphocytic Leukaemia who have relapsed following treatment or whose disease does not respond to chemo or immunotherapy. GTAC decided to award this study conditional approval on condition of some minor amendments.

Item 5: New protocol: 109 A phase I, dose-escalating trial of JX-594 (thymidine kinase-deleted vaccinia virus encoding GM-CSF) administered by intravenous infusion in patients with refractory solid tumours

The study involves the use of an oncolytic vaccinia virus, deleted for the gene encoding the thymidine kinase enzyme, which destroys cancer cells. The release of cell debris has the potential to stimulate an anti-cancer immune response. To maximise this effect the virus is carrying GM-CSF which is known to enhance the recruitment and activation of antigen-presenting cells. The drug will be given intravenously and all the patients enrolled will have metastatic cancer. After some discussion GTAC approved the study.

Item 6: Protocol: 103 A phase I study of adoptive transfer of autologous tumour antigen-specific T cells with pre-conditioning chemotherapy and intravenous IL2 in patients with CD19 positive malignancy

This study is to be carried out in patients with CD19 positive tumours. It involves introducing a retrovirus (encoding a fragment of an antibody specific for CD19) into T-cells harvested from the patient. Blood is taken from the patient and T-cells are separated out and incubated with the virus in the lab. Successfully transfected cells are separated from non-modified cells and then returned to the patient via a vein. Patients are also given IL2 (a hormone like substance that promotes the survival and proliferation of the altered T-cells) intravenously. Patients also receive a mild conditioning with chemotherapy.

In discussion, the Committee was content with the revised PIL and approval was given to this study.

7: New protocol: GTAC106: Phase I/II clinical trial of T cell suicide gene therapy following allogeneic haematopoietic stem cell transplantation

This application targets graft-versus-host disease (GvHD). This is a potentially fatal condition in recipients of bone marrow transplants that occurs when donor T cells recognise the recipients cells as foreign and mount an immune attack on the patient. The donor T-cells will be modified using a retrovirus that carries a suicide gene (thymidine kinase). This allows the modified donor T-cells to be destroyed by giving the antiviral drug Ganciclovir should the patient develop GvHD.

The Committee declined this proposal in its current state but said that they would welcome a resubmission after further consideration has been given to the protocol.

8: New protocol: GTAC107: A multicenter, randomized, double blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of BHT-3009 when administered intramuscularly to patients with relapsing remitting multiple sclerosis

The study product is a plasmid carrying the gene for myelin. Patients will be injected with the plasmid in the hope that it will dampen the autoimmune response against myelin.

The Committee gave their approval for this study.

9: Compassionate use

The issue of compassionate of gene therapy products had been discussed at the last GTAC meeting and it was agreed that an application form and guidance should be developed.

GTAC were asked to consider and comment upon the application form and accompanying guidance notes the secretariat had produced.

10: SUSAR Update

Since the last meeting there had been only one SUSAR reported, which gave no reason for concern.
The Secretariat had also received an update for an SAE.

In addition the Secretariat had received several progress/safety reviews of on-going studies which were handed to members for review.

11: Chairman's actions

This item was considered under matters arising in the morning.

12: Any other business

The Committee received a named patient extension and a substantial amendment both of which were approved.
There was also an application for exemption from the flagging project which was also approved by GTAC.

Next meeting: Wednesday, 28 September 2005

GTAC Secretariat
September 2005

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