9.3 Sample Preparation20 ml of heparinized blood (100 units preservative-free) will be obtained for 
9.21 and 9.22. Approximately 2 ml of heparinized marrow will be obtained from bilateral iliac crests for 9.23. For 
tests of blood and marrow cells, mononuclear cells will be prepared by density sedimentation using standard methods. 
10.0 STATISTICAL CONSIDERATIONS (37) 
This trial will be a Phase I study of IFN-y transduced neuroblastoma cells administered by subcutaneous injection. 
The starting dose of cells will be 1 x 107/m2. Two successive dose levels will increase the cell dose to 5 x 10^ and 
10 X 107/m2. A minimum of 3 evaluable patients who have not previously received this regimen will be entered at 
each dose level (see Section 4.2). Review of entry rate into previous phase I studies of high risk neuroblastoma 
indicates that sufficient numbers of patients are available from the three participating institutions to complete the 
study within 24 months. 
Endpoints are MTD (may not be reached) or progression of disease. Toxicity will be defined as that related to the 
cytokine or to the site of injection. 
The MTD will be defined as the highest dose that is tolerated by >2 of 3 (or 4 of 6) patients receiving that dose 
without evidence of grade 3 or 4 toxicity as defuied by the CCG Toxicity Rating Scale that is not reversible within 
28 days of stopping the treatment. Toxicity will be assessed during each treatment period using standard criteria 
(history, physic^ examination, laboratory tests). 
Laboratory correlates will be determined as described above. Results for Group 1 and 2 patients will be compared. 
Disease status will be determined for all patients at study entry and repeated at weeks 8, 24, and 36. 
Nine patients will be entered for each set of engineered cells (unless toxicity dictates more): three patients per dose 
level from both Groups 1 and 2. Each Group will be analyzed separately since MTD and laboratwy parameters may 
be influenced by ABMT. It is anticipated that 1.5-2 years will be requi^ to complete the phase I/Ib study for each 
set of engineered tumor cells. 
11.0 ADVERSE REACTION REPORTING AND TOXICITY CRITERIA 
11.1 Guidelines for Reporting Adverse Drug Reactions; The timely reporting of adverse reactions 
(including toxic deaths) is required by the Food and Drug Administration. Reactions definitely felt to be 
treatment related should not be reported; however, a repot should be submitted if there is any suspicion of treatment- 
related effect The reporting of adverse reactions is in addition to and does not supplant the reporting of toxicides as 
part of the data reporting for this study. 
11.1.1 Reporting adverse drug reactions occurring with Investigational Agents; -Within 24 
hours of recognition, contact the study Co-Chairman (Dr. Seeger or designee) by telephone to verify the 
identification pxx«ss and the existence of an adverse drug reaction ot toxic death. 
-The IND for the investigational agent will be jointly held by Dr. Joseph Rosenblatt (UCLA) and Dr. Robert Seeger 
(CHLA). 
-Upon concurrence by the Study Co-Chairman (Dr. Seeger), rqwrt the following data: 
Institution 
Patient identification number 
Presenting diagnosis 
Laboratory data supporting event 
Total dose(s) of suspected drug 
Time to event 
Type and grade of adverse event 
Methods used to recognize and characterize the effect 
-Within seven (7) days a completed NCI Adverse Reaction Form for Investigational Agents should be sent to the 
study Co-Chairman (Dr. Seeger) for all life-threatening events which may be due to drug administration, all fatal 
events while on protocol therapy, or first occurrence of any previously unknown clinical event (regardless of 
grade). The study Co-Chairman will forward this form to the FDA within ten (10) days of the adverse reaction. 
Recombinant DNA Research, Volume 19 
