8.2 Disordered hematopoiesis, abnormal morphology and alteration of 
the ratio of myeloid to erythroid cells will be established by 
morphology every three months as outlined in Appendix F. 
8.3 Neurotoxicity or mucositis (Grade III) in 3 consecutive patients 
will be grounds for decreasing the Taxol dose. 
9.0 CRITERIA FOR REMOVAL FROM STUDY 
9.1 Patients whose marrow is not successfully marked with the MDR-1 
retroviral vector, and whose marrow does not exhibit an increase 
in the level of resistance to the conventional dose chemotherapy 
with MDR drugs will not be continued on study unless there are 
preparations of marrow which contain elevated levels of 
hematopoietic cells which are resistant to MDR drugs above the 
levels which are encountered with unmodified cells. 
10.0 STATISTICAL CONSIDERATIONS 
10.1 For this pilot trial, evaluation of the persistence of the 
functional state of the MDR sequences introduced into marrow 
cells which are then transplanted will be conducted by aspiration 
of marrow cells following hematopoietic recovery from the 
transplant, and following each dose of post-transplantation 
therapy with Taxol for the first two years, or until the therapy 
is discontinued due to progression of disease, or until the death 
of the patient. PCR for MDR-1 will be used, and functional 
assays for the efficiency of afflux pumping by the marrow cells 
of dye rhodamine, or of the MDR drugs such as adriamycin, or by 
study of in vitro resistance of the modified cells. The PCR assay 
and functional assays of MDR-1 pumping will be done following the 
schedule outlined in Appendix F. The number of patients 
necessary for this program is 15-20. One patient per month will 
be evaluated and then study completed in one to two years. 
The outcome which would lead to further study is that in in vitro 
and in vivo evidence of attenuating nadirs by 50% would prompt 
their investigators to further studies. 
10.2 Evaluation of the response of the ovarian cancer to the therapy 
delivered as preparative therapy before bone marrow 
transplantation, and after the post-transplantation therapy of 
cyclical high dose Taxol, as outlined in the Treatment Plan. 
10.3 Stopping Rules: If three successive patients have treatment 
deaths or failure to engraft, delayed hematopoietic recovery, or 
any treatment-related cause, the trial will be stopped. If the 
preparative therapy or the Taxol maintenance is ineffective in 
over 5 consecutive patients, the list will be stopped. 
References 
Ozols . R.F. et al. J. Clin. Oncol. 3:1246, 1985. 
2 - Canetta, R.M. et al. J. Cancer Res. Clin. Oncol. 107 : 111, 1984 . 
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