TABLE 12 
DOSE ESCALATION SCHEME 
PARALLEL DOSE ESCALATION STUDIES 
RCC CELLS PREPARED WITHOUT 
GENE TRANSDUCTION 
DOSE 
LEVEL 
4 
1x10’ 
DOSE 
LEVEL 
3 
4xl0 ! 
DOSE 
LEVEL 
2 
4x10 
DOSE 
LEVEL 
1 
4x10' 
RCC CELLS PREPARED WITH 
GM-CSF GENE TRANSDUCTION 
1x10 9 +GM-CSF 
4x10 8 +GM-CSF 
4x10 7 +GM-CSF 
4x10 6 +GM-CSF 
L RANDOMIZED TO CELL PREPARATIO 
DOSE ESCALATION SCHEME: 
After randomization to cell preparation, patients will be assigned to a treatment position on one arm of the study. Randomization to either 
arm of the study will continue until every treatment position is evaluated, or dose limiting toxicities are observed. If one arm of the study 
completes accrual before the other, randomization will stop to expedite study completion. Each bar above represents a position to be filled. 
Starting with Dose Level 1, every patient treatment position must accrue and represent I completed, evaluable 28 day course at the Dose 
Level under study before dose escalation proceeds to the next Dose Level. If one case of dose limiting toxicity is observed in the original set 
of treatment positions at a given Dose Level, three additional patients will be treated at that Dose Level to assess whether a dose limiting 
toxicity occurs again. If no further cases of dose-limiting toxicity are observed in this additional set of 3 patients, dose escalation will 
continue to the next level. If two cases of dose-limiting toxicity are observed at a Dose Level under evaluation, 3 additional patients will be 
treated at the next lower Dose Level to confirm the MTD is approached. (Sections 3, 5, and 9) In the case of Dose Level 1, 2 cases of 
dose-limiting toxicities in a total set of 5 individual patients will close that arm of the study to further accrual. Dose Level 4 represents the 
feasible limits of short-term culture of RCC vaccine cells. Unlike the rules for the lower 3 Dose Levels, if sufficient cells are available for 
only 1 or 2 complete treatments at Dose Level 4, patients will be treated at Dose Level 4 and not dropped to a lower Dose Level to 
complete 3 courses. If no dose-limiting toxicities are observed for Dose Level 4, alter 3 patients complete at least 1 treatment cycle, 3 
additional patients will be assigned to confirm no dose limiting toxicities exist at the limits of achievable cell dose. No individual patient 
will be treated with escalating doses. Cumulative toxicity will be studied, if possible, by up to a total of 3 courses spaced every 28 days. 
In the event there is evidence of a partial response during treatment in either arm of the study, if sufficient vaccine cells remain, and if there 
is no evidence of hazardous cumulative toxicity, patients can continue beyond the 3 scheduled 28 day injections until exhaustion of prepared 
cells. However, to maintain a symmetric study of the cumulative toxicity of three cycles of injections, such a patient’s treatment position 
may be re-opened for accrual to evaluate 3 complete treatment cycles in another patient. 
CONTINGENCIES: If in preparation of vaccine cells, insufficient cells are available to complete 3 courses of treatment at the assigned 
Dose Level, the patient will be treated at the highest Dose Level allowing 3 complete courses. In this case, the treatment position will 
remain open. No dose fractions will be given. If Dose Level is dropped in this situation, the treatment position originally assigned will 
remain open for accrual, however. If after gene transfer GM-CSF secretion is below the lower limit of 24 ng/10 6 cells/24 hr, the patient 
will be treated at the assigned Dose Level and be assessed for clinical toxicity; however, the original treatment position assigned will remain 
open for accrual to treatment with vaccine plus GM-CSF gene transfer. 
Recombinant DNA Research, Volume 17 
[313] 
