clinical outcome and toxicity, and the laboratory evaluation of retrovirus insertion will be the 
responsibility of Dr. Friedrich Schuening. 
12. Statistical Considerations 
The primary endpoint of this study is to examine the safety of ex vivo retrovirus-mediated 
transfer of the human GC cDNA into peripheral blood repopulating cells of patients with type 1 
Gaucher’s disease followed by infusion of the transduced cells into the patients. The persistence and 
expression of the GC gene in hematopoietic cells after infusion will also be studied. At the conclusion 
of the study, each of these parameters will be presented descriptively. A total of 10 patients at least 18 
years of age having documented type 1 Gaucher’s disease will be enrolled onto the study. With respect 
to safety, we do not expect any adverse events like helper virus generation or retrovirus induced tumor 
development to occur. If 10 patients are treated and none experiences adverse events, then the upper 
limit of the 80% one-sided confidence interval for the true probability of an adverse event is 14.8%, i.e., 
if no adverse events occur among the 10 patients, we can be 80% confident that the true risk of an 
adverse event is less than 14.8%. 
13. Termination of the study 
No toxicities related to gene transduction were observed in patients who were treated with 
infusions of tumor-infiltrating lymphocytes which had been marked with a neo gene containing 
retrovirus vector (LNL6) very similar to the vector LgGC used in this study. The study will be 
terminated if at any time the probability of any grade 3 toxicity that is felt to be due to the gene 
therapy procedure, including the development of replication-competent murine retrovirus in patients, 
exceeds 10% as determined by the lower limit of an 80% one-sided confidence interval that exceeds 
10%. This will occur if 1/2 or 2/4-8 patients experience the adverse event. If any patient experiences a 
fatal toxicity due to the gene therapy, or develops a tumor which contains retrovirus-vector DNA or 
replication-competent virus DNA, then the study will be terminated, as any non-zero incidence of gene 
therapy related grade 4 toxicity is unacceptable. 
14. References 
1. Brady RO, Barranger JA: Glucosylceramide Lipidosis: Gaucher disease. In: Stanbury JB, 
Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS, eds. The Metabolic Basis of 
Inherited Disease. 5th ed. New York: McGraw-Hill, 1983:842-56. 
2. Beutler E: Gaucher disease. N Eng J Med 325:1354-1360, 1991. 
3. Brady RO, Kanfer JN, Shapiro D: Metabolism of glucocerebrosidase. II. Evidence of an 
enzymatic deficiency in Gaucher disease. Biochem Biophys Res Commun 18:221-225, 1965. 
4. Brady RO, Kanfer JN, Bradley RM, Shapiro D: Demonstration of a deficiency of 
glucocerebroside-cleaving enzyme in Gaucher disease. J Clin Invest 45:112-115, 1966. 
5. Hobbs JR, Hugh Jones K, Shaw PJ, Lindsay I, Hancock M: Beneficial effect of pre-transplant 
splenectomy on displacement bone marrow transplantation for Gaucher syndrome. Lancet 
1:1111-1115, 1987. 
6. Ringden O, Groth CG, Erikson A, et al: Long term follow-up of the first successful bone 
marrow transplantation in Gaucher disease. Transplantation 46:66-70, 1988. 
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