Human Gene Therapy Subcommittee - 7/30/90 
4. That a space be left on the form to indicate dosage 
being administered; 
5. That anything reported as grade 4 toxicity will be 
reported as adverse toxicity; however, the protocol 
does not clearly state that higher grades will be 
annotated ; 
6. That the "Statistics" section implies that only one 
patient will be used at a given level, whereas 
"Appendix A" states that "First patient series equal to 
or five." Therefore, it is not clear how many patients 
are to be treated at each level before escalation, and 
how many events are required before cessation of 
escalation; and 
7. That something should be placed in the protocol that 
tells how toxicity will be stopped if it is felt to be 
intolerable. 
Dr. Leventhal said she also had some comments on the consent 
form, partly in response to Mr. Capron's letter, which had been 
received over the lunch hour. She said the sentence at the end 
of the first paragraph in the consent form says that chemotherapy 
may be an option, whereas it was previously stated that 
chemotherapy would probably not work in the patient's case. Dr. 
Leventhal suggested adding a section called "Alternatives," in 
which such issues could be addressed. She suggested the 
following wording: 
"You don't have to participate in this study if you 
don't want to do so. You can go to another physician 
for therapy at any time. There is no known curative 
therapy for your disease at the present time, and you 
could choose to have no further therapy." 
Dr. Mahoney said he felt the sentence in the consent form which 
states, "If you will participate in this part of the study, we 
will transform your lymphocytes," is misleading in that the 
entire protocol is a "gene therapy protocol." It should be 
reworded to omit the phrase "If you will participate in this part 
of the study ..." 
Further Dr. Mahoney said he was not clear on what was known about 
in vitro control of cytokine secretion or expression by growth 
factors. Dr. Rosenberg said that this question had been studied 
extensively in patients receiving IL-2, alpha-interferon and TNF, 
and that in fact some cytokines can lead to secretion of others. 
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Recombinant DNA Research, Volume 14 
