Present: Professor Norman C Nevin (Chair), Mrs Debbie Beirne, Mr David Crosby, Professor Martin Gore, Professor Terry Hamblin, Professor David Harrison, Dr Peter Harris, Professor Nick Lemoine, Professor Andrew Lever, Professor Alex Markham, Rev Dr Lee Rayfield

Secretariat: Dr John Connolly, Dr Jayne Spink, Mrs Margaret Straughan, Mr Daniel Gooch

Item 1. Introduction and apologies.

The Chair welcomed Members to the 40^th meeting. A number of apologies had been received: Mrs Ann Hunt, Professors James Neil and Ian Hart, Dr Michael Waterhouse, Ms Caroline Benjamin, Mr Michael Harrison and Ms Liz Woodeson all had conflicting meetings. The MCA had also sent apologies.

Ann Hunt and Ian Hart's term of office had come to an end and the Chair thanked Mrs Hunt and Prof Hart for their contributions to the Committee. The Chair welcomed Dr Peter Harris to his first meeting.

The Chair reminded members of the last meeting where the predominant issue had been the X-SCID leukaemia case. The Committee Members were updated with respect to the regulatory position in other countries.

Item 2. Minutes of the 39^th Meeting.

With a few clarifying points, these were accepted as a true record.

Item 3. Matters Arising.

A request had been made to amend the GTAC X-SCID protocol (GTAC 045). After discussion, it was agreed that the proposers should write two new separate protocols. One to treat further X-SCID patients as established in the approved GTAC protocol and the other to treat patients using umbilical cord blood stem cells.

The Chair, Jim Heil, Alex Markham and Jayne Spink had attended a meeting of the Biological Subgroup of the Committee on Safety of Medicines at the MCA, where the X-SCID leukaemia case was discussed. It was confirmed that the working party announced on 4^th October would be a joint CSM/GTAC meeting.

In the light of the X-SCID leukaemia case in France, the Secretariat confirmed that all proposers using retroviral vectors had been asked specifically to include a paragraph in the Patient Information Leaflet on the risk of insertional mutagenesis.

Item 4. Protocol: Phase I clinical gene therapy trial for adenosine deaminase deficiency. Great Ormond Street Hospital, London

The proposal involves gene therapy for an immuno-deficiency known as ADA-SCID, which affects both boys and girls. The most successful approach to treat ADA-SCID patients involves a bone marrow transplant from a related or compatible donor. This results in immune system function (about 90 %), but compatible donors are available in only 30% of cases. Where only limited match donors are available, bone marrow transplantation is much less successful. Further, bone marrow transplants can be complicated by "Graft versus Host" disease. An alternative option, although not curative, is known as enzyme replacement therapy. The ADA enzyme is linked with a chemical called PEG (PEG-ADA) and is normally administered weekly. This provides most patients with some functional enzyme but it can cause unwanted side effects.

ADA-SCID was the first disease where gene therapy was attempted in the early 1990s. There have been a number of subsequent trials but efficacy has been limited.

After a short presentation by the proposers and discussion by Members, the proposal to use a novel retroviral vector to deliver the ADA gene to infant ADA-SCID patients was approved by GTAC. This was subject to minor amendments.

Item 5. Amendment 10: First administration to man of Trovax - Assessment of Safety, Immunogenicity, Activity and Biodistribution. Christie Hospital, Manchester.

The original study was considered in July 2000 and granted approval in October 2000. The study product is based on a virus, modified Vaccinia Ankara Virus (MVA). The proposers supplied data on the study to date and now wished to amend the study protocol to assess immunisation in conjunction with first line chemotherapy. After a short presentation by the proposers and discussion by Members, the Committee decided that this should be a submitted as a new protocol and not as an amendment.

Item 6. Amendment - Version III of a Phase I/II study of immunotherapy for patients with metastatic melanoma using dendritic cells transfected with a plasmid encoding two antigens. Birmingham University.

The original study was considered by GTAC in February 2001 and final approval was granted in November 2001. The proposers now requested a number of amendments which resulted in an increase in blood sampling. After a short presentation by the proposers and discussion by Members, is was agreed to give approval for this amendment subject to minor clarifications in the study protocol.

Item 7. Chairman's Actions.

A number of amendments had been approved since the last committee meeting. These were noted by GTAC.

Item 8. Any Other Business.

Members were presented with the latest version of the database of SAEs received since the last meeting. These were discussed in detail.

Comments by the Members on the Eighth Annual Report had been received and these had been considered by DH. The final report would be published in January.

The Report on "Human Genetics and Behaviour" by the Nuffield Council on Bioethics had been published. A recommendation in the report was that GTAC should draft specific guidelines relating to the use of gene therapy in behavioural trait modification (where behaviour is in the "normal range"). Following this report, it had been made clear by GTAC that it would not consider any proposals to carry out gene therapy for behavioural traits.

GTAC Secretariat
December 2002

Top

copyright: © | last updated 24 June 2003