Recombinant DMA Advisory Committee - 5/30-31/91 
XI. PROPOSED ADDITIONS TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
HUMAN GENE TRANSFER PROTOCOLS ENTITLED A PHASE //// TRIAL OF HIGH- 
DOSE CARBOPLATIN AND ETOPOSIDE WITH AUTOLOGOUS MARROW SUPPORT 
FOR TREATMENT OF STAGE D NEUROBLASTOMA IN FIRST REMISSION: USE OF 
MARKER GENES TO INVESTIGATE THE BIOLOGY OF MARROW RECONSTITUTION 
AND THE MECHANISM OF RELAPSE; AND A PHASE II TRIAL OF HIGH-DOSE 
CARBOPLATIN AND ETOPOSIDE WITH AUTOLOGOUS MARROW SUPPORT FOR 
TREATMENT OF RELAPSE/REFRACTORY NEUROBLASTOMA WITHOUT APPARENT 
BONE MARROW INVOLVEMENT: USE OF MARKER GENES TO INVESTIGATE THE 
BIOLOGY OF MARROW RECONSTITUTION AND THE MECHANISM OF RELAPSE: 
Dr. Brenner apologized for not being at the meeting in the morning due to a misunderstand- 
ing in meeting location. He said these protocols were similar to those proposed and approved 
at the last RAC meeting for AML, as well as the protocol of Dr. Deisseroth which was just 
discussed. 
Dr. Brenner said that children who have neuroblastoma who are over the age of one year who 
go into remission with chemotherapy almost invariably relapse. He said the aim of the study 
was to try to eradicate the minimal residual disease which causes the relapse by giving them 
intensive chemotherapy followed by autologous bone marrow transplantation. 
He said that previous experience had shown that many of these children subsequently relapse 
nonetheless and that this may be because the disease was not eradicated in the patient or that 
the marrow harvested prior to the most intensive chemotherapy contained residual tumor cells 
which have then repopulated the patient and caused relapse. He said that if it could be 
determined that the marrow contained these cells, the investigators could undertake a process 
of purging to remove those cells from the marrow before reinfusion. He noted that although 
purging techniques exist for neuroblastoma in marrow it is not known whether malignant cells 
remain in the marrow or whether the purging techniques currently available actually remove 
the malignant cells. However, if a technique of purging the marrow could be determined then 
it would make possible autologous marrow transplant with a marrow known to be safe and 
the children could then undergo multiple courses of highly intensive chemotherapy which 
could eradicate a higher proportion of minimal residual disease and actually start curing a 
higher proportion of patients. 
He said that this was an investigational protocol to some extent, but it was hoped that it could 
be moved quickly into practice to allow a therapeutic benefit by developing better 
methods of marrow purging and thereby increasing the possibility of curing a higher 
proportion of children with advanced disease. 
He said he would outline the experimental basis for the protocol and then discuss the clinical 
relevance and experimental details. 
He said it was possible to actually identify neuroblastoma cells grown from the marrows of 
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