Recombinant DNA Advisory Committee - 06/7-8/93 
Since this protocol is a Phase II study addressing the question of treatment efficacy, it is 
important to clearly state the definition of responses and criteria of efficacy. It is unclear 
how the "stop/proceed" criterion was derived. A total of 15 patients will be placed on 
this study initially. If no patients respond to treatment, then the trial will be closed. If 
at least 1 patient responds, then an additional 14 patients will be enrolled in this study. 
How were these numbers derived at statistically? What are the re-treatment criteria? 
Patients who demonstrate minimal, partial, or complete responses to therapy will be 
considered for re-treatment with 3 cycles of virus producer cells (VPC). What is 
considered a response, and what are the rationale for these criteria? If these questions 
are adequately addressed by the Pis, the protocol should be approved. 
Review-Dr. Geiduschek 
As a note on safety, the PI has indicated that 8 brain tumor patients have now been 
treated, and no evidence of toxicity has been observed. Dr. Geiduschek asked the Pis to 
confirm whether this statement is true. Most of the other points raised by Dr. 
Geiduschek concerned the wording in the Informed Consent document, such as explicitly 
stating that the cells to be given to patients are mouse cells. Dr. Geiduschek expressed 
his satisfaction to responses from the Pis on his remarks. 
Other Comments 
Dr. Zallen asked why there was no assent form included for children participating in this 
trial. Dr. Raffel stated that at the Childrens Hospital of Los Angeles the same form is 
used for consent by parents and assent by children, a practice adopted by the Committee 
for Clinical Investigation. Dr. Parkman, the past Chair of the Committee for Clinical 
Investigation, agreed with Dr. Raffel's statement. Dr. Zallen questioned whether a 10 
year old is capable of understanding the consent form prepared for adults. Dr. Motulsky 
shared the same sentiments. Mr. Capron expressed the need to prepare a form 
understandable to minors. Since different institutions have their own rules for preparing 
these documents, Ms. Meyers proposed uniform federal regulation. Dr. Walters stated 
that proposing such regulation is beyond the mandate of the RAC, but a letter could be 
drafted addressing this issue for institutions funded by NIH. 
Dr. Doi inquired whether the young animals responded similarly to adults in the animal 
studies. Is there additional information about the toxicity issue? Ms. Wilson noted that 
a report had been filed with ORDA regarding a possible adverse reaction on the 
Oldfield protocol. One patient demonstrated asymptomatic gliosis following treatment. 
Dr. Miller said that the vector used in this trial is different from the vector used in the 
previous protocols. Does this vector have the same activity as the vector used for the 
animal experiments? He asked if the Pis are planning to treat a large number of 
patients in this study before obtaining results from previous protocols. 
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Recombinant DNA Research, Volume 17 
