Recombinant DNA Advisory Committee - 09/14-15/92 
chemotherapy histories, and different cytokines for each group? At what point do the 
investigators plan to use a single patient population using three different mobilizing 
agents as the variable? Dr. Schuening responded that in the long run, this approach 
would be the best for obtaining definitive answers. However, with the patient 
recruitment levels for these therapeutic protocols, it is not possible to have sufficient 
numbers of patients to examine these variables in a systematic approach. The gene 
marking protocol must be approved as an addition to these already existing protocols. 
To date, no difference has been observed in the time of recovery from autologous 
transplantation between the various types of tumors. Dr. Leventhal noted that the 
protocol design would be improved if patients with various tumor types were given one 
particular cytokine versus one cytokine to one tumor type. Dr. Leventhal requested 
clarification as to the tumor type versus the specific cytokine that will be used. Dr. 
Schuening said that G-CSF will be administered to breast cancer and Hodgkin's patients, 
whereas IL-3 will be administered only to lymphoma patients. Dr. Murray noted that the 
protocol titles do not correspond to this fact. 
Dr. Chase said that experimental design dictates that multiple treatments for multiple 
diagnosis does not require increased numbers of patients, merely the proper allocation of 
patients. Therefore, this is not a resource question, it is a question regarding 
experimental design. 
Dr. Parkman said that the RAC must focus on the fact that this protocol is a gene 
marking study, independent of preexisting therapeutic studies. Dr. Leventhal said that if 
this trial were to be truly randomized, then representative patients from each tumor type 
should be assigned for each particular cytokine. Dr. Parkman explained that if the 
investigators are required to make this change, then they will have to change the design 
of their basic therapeutic protocols. 
Dr. Murray called on Dr. D. Miller 2 to present background information regarding the 
LN vector. Dr. D. Miller stated that LN is a modest modification of the LNL6 vector 
that has been approved for use by the RAC. LNL6 has an envelope sequence that could 
allow for homologous recombination with a packaging DNA or RNA. With LN, all of 
these env sequences have been deleted. LN is almost identical to the GINa vector 
which has an additional linker on the end. Therefore, LN should be the safest vector. 
LN is produced by Targeted Genetics, Inc. This company also supplied the vector used 
by Dr. Philip Greenberg of Seattle, Washington. Dr. Greenberg's protocol was 
previously reviewed and approved by the RAC and the FDA. 
_ 
Dr. D. Miller is a co-investigator on this protocol. His remarks are in response 
to reviewers comments. He temporarily relinquished his position as a committee 
member during this protocol. 
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Recombinant DNA Research, Volume 16 
