Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
6.1.3 STUDY DESIGN 
These studies will provide safety and efficacy data to evaluate the Neuroblastoma Bone 
Marrow Purging System in the treatment of neuroblastoma patients undergoing 
autologous bone marrow transplantation. It will be a multicenter, uncontrolled trial with 
a total of 12 patients. The expectation is to accrue 10-12 patients per year among the 
participating institutions. The study will be closed for entry after 12 patients have been 
entered and will be evaluated 24 months after the last patient is transplanted. Patients 
will be Stage D neuroblastoma patients in first or second marrow remission by routine 
histology. 
The intent of the Neuroblastoma Bone Marrow Purging System is to remove 
neuroblastoma cells from bone marrow that is to be used for autologous rescue following 
high dose chemotherapy. Gene marking of tumor cells will be used to demonstrate the 
clinical benefit of purging in neuroblastoma (see Section 6. 1.5.3). The proposal is to 
transduce neomycin resistance marker genes, contained in two closely related vectors, 
into two aliquots of marrow obtained for ABMT as treatment for advanced 
neuroblastoma. A third aliquot will remain unmarked to be used for transplantation 
should the marked marrow fail to engraft. 
Marrow will be harvested and then undergo transduction and immunomagnetic purging. 
Immunocytological assays will be used to quantitate tumor contamination pre and post 
purging. A bone marrow aspirate and biopsy will be performed prior to harvest to 
ensure that the marrow is free of tumor involvement by routine histology. Post ABMT 
daily complete blood counts, differential counts and platelet counts will be performed 
until the patient is self-sustaining. The number of days to achieve sustained engraftment 
will be recorded. 
If relapse occurs, the neuroblastoma cells will be separated from the marrow by flow 
cytometric cell sorting of cells that are negatively stained for the CD34 and CD45 
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