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Recombinant DNA Advisory Committee - 06/7-8/93 
effects due to the treatment, (2) there should be a statement about long-term follow-up, 
(3) a section about patient confidentiality, and (4) a request for autopsy. 
Investigator Response--Dr. Hesdorffer 
In response to questions about Taxol administration in this protocol, Dr. Hesdorffer 
explained Taxol is an issue separate from the transduction protocol. The purpose of this 
study is to introduce MDR-1 into CD34( + ) cells and to evaluate long-term expression 
following ABM transplantation. If patients relapse or have residual disease after ABM 
transplantation, they or their physicians can elect to enter the Taxol protocol in which 
Taxol will be administered by a dose escalation regime. The question of enhancement of 
MDR-1 expression by Taxol will be assessed in the subsequent protocol. Dr. Hesdorffer 
agreed to revise the Informed Consent document to indicate that Taxol treatment is not 
part of the initial gene transfer experiment. 
Regarding Dr. Krogstad's question about metastatic disease involving bone marrow, Dr. 
Hesdorffer said ovarian and brain tumors rarely metastasize to the bone marrow. For 
breast cancer, the PI will select patients without metastatic disease. Data suggests that 
the monoclonal antibody selection procedure eliminates the majority of tumor cells still 
present in the bone marrow. Since most patients who participate in this study have 
advanced cancer with no other alternative therapies, the additional risk is of minimal 
concern. Dr. Hesdorffer said that the Informed Consent document will be revised 
according to Mr. Capron and Ms. Meyers' suggestions. With regard to financial 
responsibility for research-related injuries, this unresolved issue was discussed when the 
protocol was presented previously. Responding to Dr. Miller's questions about RCR 
assays, Dr. Hesdorffer said that Mus dunni co-cultivation and S + L- assays have been 
performed in addition to the reverse transcriptase assays. Twenty percent of the clinical 
grade supernatant will be assayed for RCR prior to use in patients. Dr. Miller said that 
the safety assays described by Dr. Hesdorffer were not included in this submission. 
Dr. Miller said that data have not been submitted demonstrating the transduction of 
human bone marrow cells. Dr. Hesdorffer said that these data were included in the 
original submission. Drs. Parkman and Geiduschek said that the RAC should 
recommend approval of this protocol contingent on the submission of additional data. 
Ms. Grossman expressed her interest in reviewing the additional data. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Krogstad to approve the 
protocol. Approval of the protocol is contingent on the review and approval of the 
following: (1) data demonstrating the transduction efficiency of human CD34( + ) cells, 
and (2) a description of assays that will be performed on the clinical grade supernatant. 
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Recombinant DNA Research, Volume 17 
