Recombinant DMA Advisory Committee - 6/9-10/94 
with ILr2 to 100 patients before the IL-4 gene therapy trial was proposed, but extensive 
toxicology data in animal models was not required by the RAC. Dr. Parkman 
commented that this chnical scenario is different in which no human IL-7 data is 
available. Dr. Overell said that negotiations have already occurred with the FDA 
regarding the kind of toxicology data that will be required. He asked whether the data 
required by the FDA would be satisfactory for the RAC. Dr. Wivel commented that the 
FDA required data will serve the purpose. Dr. Parkman noted that a justification for the 
starting dose is necessary and the result related to scleroderma. Dr. Walters concluded 
that the toxicology study design negotiated with FDA will be acceptable to the RAC. 
Dr. Parkman said that due to the serious deficiency of preclinical data, it would require a 
new submission for the future RAC review, not just provisions of toxicology data. 
Committee Motion 
Dr. Motulsky made a motion to defer the protocol. Dr. Parkman made a friendly 
amendment that efficacy data must be provided from preexisting tumor models when the 
protocol is resubmitted. Dr. Motulsky did not accept the friendly amendment. 
The RAC approved a motion was made by Dr. Motulsky and seconded by Dr. Doi to 
defer the protocol submitted by Drs. Economou, Glaspy, and McBride of the University 
of California, Los Angeles, California, by a vote of 12 in favor, 0 opposed, and 2 
abstentions. The RAC deferred the protocol based on insufficient toxicology studies and 
failure to demonstrate biological efficacy. Dr. Parkman recommended that data 
demonstrating biological efficacy in a preexisting murine tumor model be provided when 
the protocol is resubmitted. Dr. Motulsky said that he would not require such data. Dr. 
Walters noted that Dr. Miller abstained from voting due to his collaboration with 
Targeted Genetics, Inc.. 
Chair Note 
Dr. Walters welcomed Dr. David Ginsberg of the University of Michigan as a new 
member of the RAC and Dr. Harold Ginsberg as an ad hoc consultant for the 
adenovirus protocol submitted by Dr. Jack Roth of MD Anderson Cancer Center, 
Houston, Texas. 
XV. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: CLINICAL PROTOCOL FOR 
MODIFICATION OF TUMOR SUPPRESSOR GENE EXPRESSION AND INDUCTION 
OF APOPTOSIS IN NON-SMALL CELL LUNG CANCER (NSCLC) WITH AN 
ADENOVIRUS VECTOR EXPRESSING WILDTYPE p53 AND CISPLATIN/DR, ROTH 
Review-Dr. Haselkom 
Dr. Walters called on Dr. Haselkom to present his primary review of the protocol 
submitted by Dr. Jack A. Roth of M.D. Anderson Cancer Center, Houston, Texas. Dr. 
Haselkom explained that this protocol involves the in vivo transduction of wildtype p53, 
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