6.0 REGISTRATION OF PATIENTS 
All patients eligible for this phase I study will be discussed and 
evaluated by the principal investigator and co-investigators before entry into 
the study. Alternatives to participation, including treatment with approved 
systemic IL-2, or phase I agents will be considered. The on-study 
requirements for clinical laboratory work, baseline immunological studies, and 
clinical evaluation are to be completed and entered into Biostatistics Office 
trial computerized data base 5 days before Day 0 of Stage 2 of the trial. 
7 . 0 STUDY PARAMETERS 
7.1 RATIONALE FOR CLINICAL TOXICITY EVALUATION 
This treatment is not a cytotoxic drug. No dose limiting toxicities may 
be observed even at Dose Level 4. Nevertheless, the common toxicity criteria 
of the NCI and the cutaneous toxicity scale unique to this trial described in 
Appendix 14. E and Appendix 14. F will be employed. After treatment, patients 
will be seen as outpatients on a frequent scheduled basis. After 3 cycles of 
treatment are ended (day 84), patients will be followed in Stage 3 of the 
study, and return for scheduled evaluations or sooner as clinically indicated. 
7.2 RATIONALE FOR IMMUNOLOGIC STUDIES 
As described, the concepts being tested in this study were derived from 
murine model systems that enabled screening of a number tumor/cytokine 
combinations for efficacy. This allows for initial dissection of the 
underlying immunological mechanisms responsible for the observed anti-tumor 
effects. One objective of the current study is to determine the validity of 
the mouse model systems as predictors of anti-tumor immunological activity in 
humans . 
The "gold-standard" measure of the anti-tumor immune response in the 
murine model is protection against or cure of a defined live tumor challenge. 
If in stage IV renal cell tumor patients, metastatic regression following 
treatment is not observed, this may not mean that the cell therapy is 
inactive, rather, that the "readout" at high tumor burdens is too insensitive 
to show the presence of an active anti-tumor immune response. In fact, it is 
likely this may be the case in this phase I study using patients with advanced 
RCC, and that significant immunologic activity could be missed if tumor 
response were the sole criterion of potential therapeutic activity. 
Consequently, our preclinical studies have focused on a variety of 
measurements that characterize the specific features of the antitumor immune 
response to GM-CSF transduced tumor vaccines. These enable an attempt at 
correlation with overall protection against tumor challenge, as well as giving 
some insight into the immunologic mechanism underlying the observed effect. 
Accordingly, these measurements will be made in patients treated in the 
current study. 
I 
Recombinant DNA Research, Volume 17 
[325] 
