June 1, 1990, Human Gene Therapy Subcommittee Minutes 
discussed by the IRB and found to be a minimal risk procedure. Mention is made that, 
"the patient may experience chills, fever, tachycardia, nausea and vomiting; potential 
risks include cardiac arrhythmias, vascular thrombosis and pulmonary embolus." He said 
that would not constitute "minimal risk" in his IRB. However, the NIH IRB might 
consider them as such. 
Dr. Leventhal asked whether there was any experience in giving IP infusions in 
immunosuppressed patients. Dr. Parkman said there was experience in the 1970s that 
showed IP injection to be only one-tenth as efficacious as IV administration. If the IV 
injection did not work, the investigators should return to the HGTS with more preclinical 
data on IP administration, given the potential risks of IP administration and the fact that 
it has been proven to be less efficacious. Moreover, he said that he did not characterize 
this protocol as "minimal risk," but rather as "unknown risk." He also noted a significant 
difference between this protocol and the N2/TIL protocol in that the life expectancy of 
the study participants is much longer. Therefore, safety and efficacy are much more 
important issues. This requires more long-term follow-up and life-long assessment of the 
patients. The frequency of follow-up studies needs to be better defined. 
Dr. Parkman also said the informed consent must take into account the possibility of 
therapeutic failure and the necessity for the patient to become a life-long research 
subject. This has to be understood, and the patient must be aware of it if the study is to 
derive the maximum benefit from these patients. 
Dr. Walters thanked Dr. Parkman for both his general comments on bone marrow 
transplantation and for his primary review. 
Dr. Walters asked Dr. Parlonan to define for the subcommittee what he considered the 
major changes in the new version of the protocol, as compared with the previous version. 
Dr. Parkman said that the hypothesis of the insertion of the ADA gene into the T cells is 
more completely spelled out and additional preclinical data have been presented. 
However, the issue of levels of activity of detoxification of deoxyadenosine metabolites 
has not been expanded. The clinical protocol is more defined, with the major issue 
being identification of children not qualifying for bone marrow transplantation requiring 
cytoreduction and the necessity for children who are stable. The issue of dealing with 
these two groups as separate entities needs to be more clearly defined. He added that a 
major step forward is the preclinical data that transduced T cells appear to be capable of 
specific in vivo immunological function. In addition, there is clarification of the clinical 
protocol in terms of patient selection, but the issue of follow-up is still not well defined. 
Dr. Walters noted that part three of the protocol was withdrawn. Therefore, the 
subcommittee was only dealing with parts one and two of the original protocol. 
Dr. Anderson clarified that the NIH IRB approved the protocol as "research involving 
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