likely to be produced in vivo in this study have not caused any 
measurable side effects in treated patients.^ 1 
4.8 Risk Management 
The risks to patients and health care professionals from the blood drawing will be 
minimized by careful attention to technique and close follow-up. The theoretical risks 
associated with gene therapy will be minimized by manufacturing practices and procedures, 
and quality control testing. 
Adverse reactions associated with product administration will be treated symptomatically by 
the principal investigators. If any subjects experience adverse reactions which are 
incapacitating or life threatening, the appropriate interventional therapy will be 
administered. If recurrent grade 3 or greater BRMP toxicity is encountered, further 
administration of HIV-IT (V) will be suspended, and a replacement subject will be admitted 
into the study. If repeated grade 3 or greater toxicity is encountered, modifications in this 
study will be implemented as set forth in Section 4.8.1 below. 
An independent monitoring board will have access to all safety data and to the product 
administration code. This monitoring board will evaluate adverse events to ascertain 
whether such events are related to treatment group or dosage and whether toxicity grade 
limits have been reached that would require dosage modification (see Section 4. 8.1). 
4.8.1 Impact of Adverse Reactions on Study Plan: Dosage Modification 
Schedule 
4.8. 1. 1 If recurrent grade 3 or greater BRMP toxicity (see Section 4.14.0) is 
observed in three patients receiving the lower dose of HIV-IT (V), this 
study will be suspended. 
4. 8 . 1 . 2 If recurrent grade 3 or greater BRMP toxicity is observed in three 
subjects receiving the highest dose of HIV-IT (V), the remaining 
subjects will receive HTV-IT (V) at the lower dosage level (10^ cfu). 
Red field R.R. et al, N. E. Journal of Med., 324:1677-1684 (1991). 
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