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6.0 TREATMENT MODIFICATION AND DISCONTINUATION ACCORDING TO LEVEL 
OF TOXICITY 
Appendix II is the Toxicity Grading Table and Appendix III is the Adverse Experiences 
Reporting Guidelines. 
The GTI Table for Grading Severity of Adverse Experience (Appendix II) will be used to 
achieve consistency in response to drug/treatment toxicities. Toxicities will be graded on a 1 - 
4 grading scale. If a toxicity is experienced, the treatment level or dose will be modified (if 
applicable) as outlined below according the grade of toxicity observed. 
6.1 Treatment Modification According to Level of Toxicity (Generali 
• For any Grades 1-2 toxicity, there will be no dose modification. However, 
repeat tests to confirm values within 72 hours may be required. 
• Any Grade 3 toxicity, thought to be related to G-CSF, will necessitate a 50% 
dosage reduction. If a Grade 3 toxicity persists for seven days or advances to 
Grade 4 toxicity, G-CSF will be discontinued and the patient will not re-start the 
medication. The patient will continue to have apheresis as if G-CSF were 
administered for the current cycle only. The patient will receive no further G- 
CSF and therefore no further cycles of peripheral stem harvest will be attempted 
under this protocol. 
• For Grade 3 toxicity not related to G-CSF, the investigators and sponsor will 
discuss the various options available. The appropriate action relative to the 
patient with a Grade 3 toxicity will be evaluated. If appropriate, a decision of 
whether the study should be continued will be recommended (see Section 7.2). 
Since no toxicities have been seen in other gene transfer protocols, precedence 
for the appropriate action is not available and will need to be decided on a case- 
by-case basis. 
6.11 Management of Specific Toxicities 
Adverse reactions to apheresis : Reactions are rare, and include anxiety, vasovagal 
reactions, and cutaneous paresthesias related to citrate-induced hypocalcemia. 
Sedation, volume repletion, and slowing of the infusion will correct these 
problems. Bleeding and infection at the line insertion site are potential 
complications of apheresis catheter placement. 
6.2 Symptomatic Therapy for Toxicity 
Symptomatic therapy such as analgesics or other helpful therapy may be administered if 
deemed necessary by the participating investigators. All medications administered will 
be recorded in the appropriate Case Report Form. 
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Recombinant DNA Research, Volume 17 
