9.0 TOXICITY EVALUATION AND DEFINITIONS 
9.1 Definitions 
The following toxicity definitions and criteria will be used in this 
phase I study. 
9.1. a. Although this therapy is not a conventional cytotoxic 
drug, the National Cancer Institute's Common Toxicity Criteria used for phase 
I evaluation of cytotoxic drugs will be used (Appendices 14. E and 14. F). In 
addition, dermatologic toxicity measurements of injection site (Appendix 14. E) 
will define special criteria for toxicity grading at the site of injection. 
9.1. b. Subtoxic Dose — a dose that causes consistent changes of 
c l^- n ^- ca l parameters of toxicity and might herald toxicity at the next highest 
Dose Level or with repeated administration. This would include a dose at 
which consistent Grade 1 toxicities are seen. 
9.1. c. Minimal Toxic Dose - the smallest dose of tumor cell 
vaccine at which one or more of the patients shows consistent, readily 
reversible clinical toxicity. In general, this will be toxicity of Grade 2 
severity, though in some cases (renal, cardiac, neurotoxicity), Grade 1 
toxicity will apply. 
9.1.d. Maximum Tolerated Dose (MTD) - the highest safely 
tolerated dose of RCC tumor cell vaccine injected on each treatment arm of the 
study in Stage 2. This will be at a Dose Level where consistent unacceptable 
toxicities are observed. Toxicities at the MTD should be reversible and 
should not subject patients to excessive risks or discomfort. Generally, 
consistent hematologic, or non-hematological toxicity of Grade 3 or 4 severity 
wit* define the MTD, but in some instances, Grade 2 toxicity may also be 
unacceptable (e.g. renal, pulmonary, neurologic, cardiac, or Grade 4 local 
injection site toxicities). Conversion of patients to antinuclear-antibody 
positivity, rheumatoid factor positivity, any clinical evidence of autoimmune 
disease (including induction of glomerulonephritis) are defined as Grade 3 
toxicities . 
9.1. e. Recommended Phase II Dose Levels -will be one Dose Level 
below the MTD if one is approached. Escalation beyond the recommended phase 
II doses would result in unacceptable, but reversible, toxicity. 
Considerations such as discomfort to the patient and evidence for any 
cumulative and/or irreversible vaccine effects (late auto-immunity) will 
obviously enter into a final determination of the optimal dosages for the 
phase II studies. 
9 . 1 . f . Death on Study - if a patient expires while on study, an 
autopsy authorized by advanced directive of the patient or by family consent 
will be sought in every case. Autopsy will be provided at no cost to the 
family to make histopathological correlations with the clinical data. 
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