Recombinant DNA Advisory Committee - 06/7-8/93 
part of the gene therapy protocol, which will be performed as part of another Phase I/II 
study, the RAC must discuss how the issue of toxicity related to Taxol administration will 
be considered. 
Review--Dr. Krogstad 
Dr. Krogstad stated that one major concern is the possibility of inadvertent transduction 
of malignant cells in the marrow. Sensitive techniques detect bone marrow metastases in 
30 to 50% patients of advanced breast cancer. Originally, he suggested that a "spiking" 
experiment be performed to simulate the inadvertent transduction of tumor cells in bone 
marrow. If tumor cells are not detected following isolation of CD34( + ) bone marrow 
cells that have been deliberately added to the initial sample, the risk of inadvertent 
transduction of tumor cells is minimal. The PI has performed such experiments, and the 
results are encouraging. The CD34( + ) cell selection procedure efficiently removes 
contaminating tumor cells from bone marrow. The Informed Consent document should 
be revised to avoid the suggestion that the present procedure is "safe", and should 
suggest that contraception should be used by males and females. The revised protocol is 
substantially improved over the previous submission. 
Review-Mr. Capron 
Mr. Capron stated that the question of whether Taxol will be involved in the present 
study is somewhat ambiguous in the writing of the protocol and the consent form. The 
headings and some technical terms of the Informed Consent document should be revised 
in simplified language. 
Other Comments 
Dr. Miller expressed concern about the RCR testing data that was submitted. The Pis 
state that an extremely safe packaging cell line will be used that is incapable of 
producing wild-type retroviruses; and therefore, does not pose any public health hazard. 
The seriousness of RCR testing has been greatly overlooked. The reverse transcriptase 
assay is not as sensitive as other retrovirus rescue assays for the detection of RCR that 
have been approved by the RAC. In this protocol, a large volume of retrovirus 
supernatant will be used to infect bone marrow cells; however, RCR assays were 
performed with 1 ml aliquots. Dr. Miller stated that these assays are unacceptable. Dr. 
Miller said that the Informed Consent document does not clearly state whether the study 
involves Taxol administration. He agreed with Dr. Parkman's concern about ambiguities 
in the scope of this study. 
Ms. Meyers said that she had the following concerns about the Informed Consent 
document: (1) the statement that patients are responsible for costs associated with side 
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