Recombinant DNA Advisory Committee - 03/1-2/93 
Review— Dr. Leventhal 
Dr. Walters called on Dr. Leventhal to present her primary review of the protocol 
submitted by Dr. Albert B. Deisseroth of the University of Texas M. D. Anderson 
Cancer Center, Houston, Texas. The objectives of this Phase I study are: (1) to test the 
feasibility of introducing the MDR-1 cDNA into normal hematopoietic early progenitor 
cells in advanced ovarian cancer patients by in vitro transduction with a retrovirus vector, 
and (2) to determine the effect on hematopoietic function following ABM 
transplantation. 
Dr. Leventhal explained that the present protocol is similar to other studies reviewed by 
the RAC. The investigators will attempt to introduce the MDR-1 gene into ABM cells 
prior to transplantation so that higher doses of Taxol can be tolerated by the patient. 
Ovarian cancer rarely metastasizes to bone marrow thus lessening the chance that drug- 
resistant tumor cells will be introduced into bone marrow. There are several concerns 
that should be addressed regarding this protocol. In vivo murine data demonstrates that 
mice which receive transduced marrow cells recover more rapidly than those that receive 
untransduced cells. Dr. Leventhal asked if in vitro assays have been performed using 
human bone marrow cells. What is the transduction rate? What is the level of MDR-1 
gene expression? The investigators need to provide a more detailed description of the 
vector, packaging cell line, and the reproducibility of experiments using the CD34( + ) 
stem cells. The procedure for harvesting nucleated ABM cells should be described. Can 
7 x 10 s CD34( + ) cells be reproducibly selected from 2 x 10 8 nucleated cells/kg? The 
protocol states that a total of 4 x 10 8 nucleated cells/kg will be harvested so that one-half 
of the cells can be cryopreserved as a back-up. Will harvesting this number of cells 
place patients at increased risk without blood transfusion? What is the relationship 
between G-CSF and Taxol administration? Is there any risk of toxicity in patients who 
have received prior anthracycline therapy with a daily dose of Cytoxan? What is the end 
point of the protocol? 
Review— Dr. Dronamraju 
Dr. Dronamraju expressed concern about the informed consent document. The 
document does not clearly state that there will be no direct benefit to the patient, 
however, useful information will be obtained for the treatment of ovarian cancer in the 
future. The document should contain a request for autopsy. 
Other Comments 
Dr. Parkman asked about the parameters that will be used to define recovery of 
hematopoietic function following each administration of Taxol. Will the proposed dose 
of Taxol be tolerated by patients following ABM transplantation? Is Taxol a standard 
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