C. No response- any patient not manifesting a complete or partial 
response . 
9.0 REPORTING OF ADVERSE REACTIONS 
All side effects per course will be graded using the standard toxicity 
sheet used in prior immunotherapy protocols presented in appendix 18.7. 
Adverse reactions will be reported promptly to the Investigational Drug Branch 
at (301) 496-7957. Reports are required even if there is only a suspicion of 
an adverse effect. Previously unknovm grade 2 and grade 3 reactions will be 
reported to the NCI in writing using the "NCI Adverse Reactions Form for 
Investigational Agents" within 10 working days. Grade 4 (life-threatening) 
reactions and patient deaths while on treatment will be reported to NCI by 
phone within 24 hours. A written report will follow within 10 working days. 
Written reports will be sent to: 
Investigational Drug Branch 
Cancer Therapy Evaluation Program 
P.O. Box 30012 
Bethesda, Maryland 20824 
Copies of adverse reactions reports will also be sent to the RAC. All 
adverse reactions should also be reported to the IRB. Data will be submitted 
to CTMS at least once every two weeks. The NCI/DCT case report or ACAS will 
be used to report to CTMS. 
10.0 POTENTIAL RISKS OF IL-12 ADMINISTRATION AND RETROVIRAL-MEDIATED GENE 
MODIFICATION 
10.1 Possible risks of IL-12 
In murine studies, we have seen essentially no toxicity in doses of 
recombinant murine IL-12 when administered dally i.p. or s.q. for as long as 
seven days in C57BL/6 mice. Similar studies carried out by Brunda et al (1994) 
for up to 30 days with administration of IL-12 for five out of seven days 
again show effectively no major toxicity. Modest elevations in transaminase, 
reduction in serxun protein and albumin and mild leucopenia and 
thrombocytopenia are observed. At the conclusion of IL-12 therapy there is no 
rebound phenomenon but rather a return to normal levels of formed elements. 
Extramedullary hematopoiesis and anemia (approximately 20% reduction in Hct at 
Decreased appetite and body weight as well as mortality were observed only at 
doses > or - to 500 mg/kg/day. 
In primate studies, mortality in a single cynomologus monkey was 
observed after seven days of treatment with 50 mg/kg/day (T. Anderson, 
Hoffmann-La Roche). In squirrel monkeys, doses up to 50 mg/kg/day were well 
tolerated. Some evidence of weight gain attributable to a vascular leak 
phenomenon, and formation of antibodies to hrIL-12 in these animals were 
observed. Toxic i ties in the other cynomologus monkeys revealed only very mild 
toxicity at the 1 mg/kg/d x 14 days dose with minimal loss of appetite and 
diarrhea at the 10 mg/kg/day dose. Mild (less than two fold) eleveations in 
hepatic transaminase was noted at the 1 mg/kg/day level. Preliminary findings 
in cynamologus monkeys (Data on file, Genetics Institute) showed that 
following the single IV bolus, serum concentrations of IL-12 exhibited a 
multiphasic decline with an apparent terminal half-life ranging from 
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