It is understood that the performance of an individual study or test as specified 
in this protocol is subject to factors such as patient compliance, scheduling 
difficulties, equipment malfunction, or the clinical judgement of the principal 
investigator or the patient care physician, and that a test therefore may not be 
done in an individual instance with no violation of the protocol. However, any 
systematic modification of the original protocol in this regard, whether related 
to patient safety or not, will be submitted to the IRB for approval. 
4. Criteria for response. Complete response is defined as the 
disappearance of all clinical evidence of disease for at least four weeks. 
Partial response is defined as the 50% or greater decrease of the sum of the 
products of perpendicular diameters of all lesions lasting at least four weeks 
with no increase in existing lesions or appearance of new lesions. Any patient 
having less than a partial response is considered to be non- responsive to 
treatment . 
5.0 POTENTIAL SIDE EFFECTS AND REPORTING OF ADVERSE REACTIONS . 
1. Reporting of adverse reactions . Adverse drug reactions (ADRs) to the IND 
Drug will be reported promptly to the Investigational Drug Branch. ADR reports 
are required even if there is only a suspicion of a drug effect. (Call IDB at 
301-496-7957) . 
Previously unknown 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 
All adverse reactions should also be reported to the IRB. 
2. Side Effects of IL-2 and IL-4 A variety of side effects have been associated 
with IL-2 administration. We have had experience with the use of high-dose IL-2 
either alone or in combination with cells or other cytokines in 1,039 courses in 
652 patients. A listing of the side effects and their incidence is presented in 
Table 5. A listing of the side effects of IL-4 in 73 patients is presented in 
Table 6 Phase lA, IL-4 qd; IIB, IL-4 tid; II, IL-4 and IL-2). 
All side effects will be graded using the standard toxicity sheet used in 
prior IL-2 protocols presented in Appendix B. 
3 . Potential risks of retroviral mediated gene modification (29) . 
a) Insertional mutagenesis . The Moloney murine leukemia virus used in this 
vector construct can cause T cell lymphomas in certain strains of mice. The 
possibility of causing malignancy in cells secondary to the random insertion of 
the retroviral vectors in the genome exists , though the actual risk of this 
occurring is thought to be low. 
The design of the proposed protocol, however, includes time for extensive 
testing of TIL following exposure to the retroviral vector prior to infusion into 
the patient. Tests of the viral supernatant as well as of the actual TIL used 
Recombinant DNA Research, Volume 14 
[847] 
