Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
likely that residual cells in both the recipient and the graft contribute to relapse, although 
the relative contribution of each is still unknown. 
6. 1 . 1 .5 Rationale For Therapy 
Concern over the demonstrated high incidence of marrow involvement in neuroblastoma, 
combined with the difficulty in achieving complete remission prior to bone marrow 
harvest and ABMT, have lead both the POG and CCSG to incorporate ex vivo bone 
marrow purging into their clinical protocols. The method of choice is immunomagnetic 
purging, in which the neuroblastoma cells are identified using a panel of monoclonal 
tumor-directed antibodies which are then eliminated by attachment to paramagnetic 
microspheres, and passage of the marrow through a magnetic field. This method is 
capable of removing 3-4 logs of neuroblastoma cells in preclinical studies (Moss et al, 
1992). 
Demonstration of this in clinical studies has to date not been possible due to the usually 
low infiltration of tumor cells into bone marrow and the limited sensitivity of detection 
methods (Moss et al, 1991). The number of patients available for study each year is less 
than 100, and it has been determined that a prospective randomized study to detect the 
clinical efficacy of purging would take more than two decades to complete. Clinicians 
have also indicated that they would be unwilling to undertake such a study for ethical 
reasons. They feel that it is unacceptable to return tumor cells to the patient, if there 
exists a method for their removal, which does not add significant risk or toxicity to the 
transplant procedure. For these reasons, a Phase 2, multicenter, uncontrolled study is 
proposed to evaluate safety and efficacy. 
The proposed study will be a Phase 2 clinical study. Previous studies performed on 
greater than 150 neuroblastoma patients have established the safety of bone marrow 
purging in autologous transplantation (See Section 9). Further, many of these studies 
employed magnetic microspheres and antibodies identical to or comparable to those 
Recombinant DNA Research, Volume 16 
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