We will calculate the mean of nine measurements of proviral copy number both before and 
after each cycle of chemotherapy. Amplification of transduced cells will be defined as an 
increase in the mean copy number at a two tailed value of p=0.05 or less. 
Although the primary endpoint of this trial will be the percentage of blood cells that contain the 
MDR-1 provirus post-transplant and following taxol therapy, we will review the severity and 
duration of myelosuppression with each cycle of chemotherapy. The nadir counts for each 
patient will be correlated with changes in the mean proviral copy number. A beneficial effect 
of MDR-1 gene transfer in ameliorating myelosuppression would be expected only if a 
substantial amplification of the transduced cell population occurs with repeated cycles of taxol 
or vinblastine. 
Ten to twelve patients per year will be treated on this pilot trial. A maximum of 18 patients 
will be treated. Consideration will be given to treating fewer than 18 patients if no gene 
marking of the marrow or peripheral blood occurs in the first 6-8 patients treated with post- 
ABMT taxol or vinblastine. This study will be stopped if the first 2 patients fail to engraft or 
if 2 patients fail to engraft during the duration of the trial. 
10.0 Off-Study Criteria 
10. 1 Progressive disease while receiving taxol or vinblastine therapy post-ABMT. 
10.2 Recurrent grade 3 or 4 toxicity with taxol or vinblastine therapy post-ABMT. 
10.3 Patients may be taken off-study by the Principal Investigator if it is deemed medically 
inappropriate to continue with therapy. 
10.4 Patients may choose to withdraw from study at any time. 
11.0 Reporting of Data and Adverse Drug Reactions 
This study will be CTMS monitored. Data will be submitted to CTMS at least every 
two weeks. The NCI/DCT Case Report or ACES will be used to report to CTMS. 
Reporting of adverse drug reactions (ADR) will be made using the Division of Cancer 
Treatment Common Toxicity Criteria and Toxicity Criteria for ABMT Studies Supplementary 
Toxicity Criteria (Appendix V) for reference according to the guidelines published by the 
DCT, NCI. The ABMT Toxicity Criteria will be the primary guideline with the Common 
Toxicity Criteria used as a supplement. Report by telephone to IDB within 24 hours (301-230- 
2330, available 24 hours per day) the toxicities below. A written report should follow within 
ten working days to: Investigation Drug Branch, P.O. Box 30012, Bethesda, Maryland 
20824. Adverse Drug Reactions must also be reported to the Chairman, ICRS at the same 
time as IDB. Reporting guidelines are summarized as follows: 
All life-threatening events (Grade 4, except for Grade 4 myelosuppression) which may 
be due to administration of investigations drug(s). 
All fatal events (Grade 5). 
All first occurrences of any previously unknown toxicity (regardless of grade). 
12.0 Response Criteria 
Complete Response: No evidence of disease on restaging one month after bone marrow 
transplant persisting for 4 weeks. 
Partial Response: A 50% or greater reduction in the size of measurable lesions as defined by 
the sum of the products of the longest perpendicular diameters of all measurable indicator 
lesions for at least one month. 
Minor Response: A 25% to 49% reduction in the size of the measurable lesions as defined by 
the sum of the products of the longest perpendicular diameters of all measurable indicator 
lesions for at least one month. 
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Recombinant DNA Research, Volume 18 
