Human Gene Therapy Subcommittee - 11/21-22/91 
the patient and follow-up procedures outlined in the informed consent document. Dr. R. 
Murray recommended approval, but requested that continued treatment only be 
approved if there is clear evidence of tumor regression. Dr. Epstein noted that since the 
protocol was for Phase I trials, it had its own built-in stopping criteria, and that the 
recommendation would not pertain to Phase II or III trials. 
Review--Dr. Childress 
Dr. Walters asked Dr. Epstein to summarize the written review submitted by Dr. 
Childress. Dr. Epstein said that the review was favorable but recommended several 
minor modifications to the informed consent document. 
Other Comments 
Dr. Parkman commented that since this protocol would be the first time that genes 
would be directly inserted into humans, the HGTS should address post-mortem studies 
to be performed in the unfortunate event that a patient should die following treatment 
due to progression of the disease. Invaluable information could be obtained from post- 
mortem tissue samples. PCR analysis of the reproductive organs (ovaries and testes) 
could demonstrate whether germ-line gene transfer had occurred. 
Dr. Leventhal said that the investigators had made a number of changes to the protocol 
which was originally presented to the HGTS. She asked for clarification concerning 
exactly what the patients would be receiving. In the future, changes such as these should 
be added as formal amendments to protocols to avoid confusion. If the HGTS asked for 
a change in methods, for example, the investigator should submit an entire revised 
methods section incorporating these suggestions. Dr. Walters noted that Dr. Nabel had 
submitted changes to the protocol in the form of bold print. Dr. Parkman said that 
requested information concerning autoimmunity testing has been included and 
highlighted in bold print. 
Dr. Leventhal said that in the Study Design and Nature of Procedures sections of the 
protocol, the investigators should have stated what vectors they intend to use and to 
address whether heart tissues were examined at the times electrocardiograms (EKGs) 
were performed in the animal experiments. Dr. Mclvor asked if the germ-line tissues 
were analyzed by PCR in the animal studies. 
Dr. Miller asked Dr. Nabel why the HGTS received additional sequence data. Dr. 
Nabel responded that this new sequence information was complete and clarified some 
ambiguities that existed in the original protocol. Dr. Miller said that vector sequence 
information submitted on paper could not be easily scanned for open reading frames. 
Investigators should supply vector sequences on computer disks prior to the meetings. 
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