Human Gene Therapy Subcommittee - 4/5/91 
obtaining a scientifically meaningful outcome. 
Dr. Leventhal saw little risk in the protocol. However, she is uncomfortable with not 
having the same in vitro procedures done on the marrow to be cultured and the marrow 
which will be reinfused. There needs to be some concern for the issue of determining 
the source of relapse of organ-specific disease which cannot be biopsied. 
Dr. Brenner noted that the FDA requires data on the percentage transduction efficiency 
of the malignant cells of the pre-infusion marrow. Further, a biopsy cannot be justified 
for the sole purpose of showing that marked cells are present. Over 65% of patients are 
expected to have bone marrow relapse or accessible biopsy relapse based on experience 
with this patient population. 
Dr. Erickson moved that the protocol be tentatively approved pending a review by Dr. 
Leventhal of detailed protocols of in vitro marrow characterization. Dr. Kelley seconded 
the motion. 
Dr. Mclvor asked Dr. Brenner if he had set a minimum level of transduction for the in 
vitro tests. Dr. Brenner said that in discussions of the AML protocol, it was decided that 
it was not wise to set a minimum level, since the nature of the repopulating cell was 
unknown. Zero percent marking in vitro might not match the in vivo events. However, if 
the subcommittee wishes to set a minimum level, he indicated his willingness to accept it. 
Dr. Leventhal asked if approval of this motion meant that the subcommittee was also 
approving the second protocol for patients who have had relapse or refractory 
neuroblastoma. Dr. Erickson said there needs to be a separate motion, but that he was 
willing to offer the same motion for the second protocol. 
Dr. Leventhal said she would be willing to make the review with the proviso that an 
early stopping rule be devised. If it is apparent after a few patients that the investigators 
are able to predict growth in vitro, they need not continue the protocol to 12 patients 
with the knowledge that the marrow being reinfused is definitely contaminated. 
Dr. Erickson accepted this as a friendly amendment to his motion. Dr. Kelley accepted 
the amendment as the seconder. There was a brief discussion of the actual number of 
positive results necessary to invoke the early stop rule, and it was determined that this 
information would be supplied to the members of the subcommittee in advance of the 
meeting of the RAC. 
Dr. Walters called for a vote on Dr. Erickson's motion to provisionally approve the 
protocol with the stipulation that reviewers further evaluate Dr. Brenner's procedures for 
in vitro bone marrow assays to detect residual tumor. Second, a provision for early 
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