Recombinant DNA Advisory Committee - 03/1-2/93 
therapy at M. D. Anderson Cancer Center for ovarian patients who have received ABM 
transplantation? 
Ms. Meyers said that the informed consent document is not understandable to the lay 
person. 
Presentation-Dr. Deisseroth 
Dr. Deisseroth responded to questions raised by Drs. Leventhal and Parkman regarding 
Taxol administration in combination with ABM transplantation. Dr. Deisseroth stated 
that Taxol is not a standard therapy for ovarian cancer. Data demonstrates that Taxol 
can be administered to only 50% of all individuals because of myelosuppressive effects. 
The rationale for this protocol is that transduced hematopoietic cells with MDR-1 will 
increase the patient's tolerance to Taxol. With regard to the safety of Taxol 
administration in combination with ABM transplantation, Drs. Deisseroth and 
Kavanaugh explained they have had experience with patients who have received Taxol 
following an ABM transplant. Back-up marrow will be stored in the event that patients 
exhibit unusual sensitivity to Taxol. 
Dr. Deisseroth presented in vitro human data that was not previously submitted. Taxol is 
routinely used to treat patients with advanced cancer. Unfortunately, therapeutic doses 
have been shown to induce severe leukopenia. At 250 mg/m 2 , 67% of patients have 
demonstrated severe neutropenia. Myelosuppression is the major obstacle to the use of 
Taxol in ovarian cancer. The goal of this study is to assess whether introduction of the 
MDR gene into hematopoietic progenitor cells will decrease Taxol sensitivity. Ovarian 
cancer was chosen as the target disease because bone marrow involvement is rare. 
The MDR cDNA contained in the vector (obtained by Dr. Michael Gottesman of the 
National Cancer Institute) has a point mutation which does not affect its function on 
drug efflux. The vector is derived from the LN vector series. 
In response to Dr. Leventhal's question, Dr. Deisseroth stated that the second bone 
marrow harvest is necessary. Dr. Deisseroth stated that they have successfully 
established a procedure for selecting CD34(+) cells using a monoclonal antibody 
column. Following MDR transduction, the bone marrow cells were cryopreserved. The 
threshold for hematopoietic recovery following the preparative regime is 100,000 
platelets per cubic microliter and an absolute neutrophil count of 2,000. Escalating 
doses of Taxol will be administered every 3 to 4 weeks in combination with MDR-1 
transduced ABM cells. Is there a stopping rule for the trial, at doses 150 mg/m 2 of 
Taxol? GM-CSF is necessary to stimulate recovery. 
FACS analysis will be used to monitor CD34(+) cells following transplantation. 
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