5.0 PLAN OF CLINICAL STUDY 
5.1 Specific Inclusion and Exclusion Criteria for Gene Transduction Eligibility 
(see section 10). 
To ensure that sufficient marrow can be purged without potentially 
compromising the rate of reconstitution should an unpurged backup marrow 
need to be given, the minimum quantity of marrow mononuclear cells to be 
obtained at harvest will be 4 x 10 8 /kg. 
Should this safety margin not be attainable, the patient will be ineligible for 
the double transduction/purging study and will be treated off protocol as 
follows:- 
If >3 but <4x 10 8 cells/kg are harvested, the marrow will be purged with 
4HC after 10 8 cells/kg are cryopreserved as a backup. 
If > 1 but <3x 10 8 cells/kg are obtained the patients will receive unpurged 
marrow 
If < 1 x 10 8 cells/kg are obtained the patients will be re-harvested at a later 
date. 
5.2 Preparation of Marrow 
Details are provided in technical appendices A and B and shown in 
diagrammatic form below. In brief, a marrow mononuclear cell fraction will 
be obtained using a Stericell separator. Two thirds of these cells will be used 
for cell free vector transduction and purging. The remaining marrow will be 
processed and frozen as per standard techniques. The marrow for 
transduction and purging will be divided in two aliquots, one transduced with 
LNL6 and one with GIN. Each will be transduced at a multiplicity of 
infection of 10:1 for 6hrs. Each aliquot will then be assigned at random for 
purging with IL2 or with 4HC. IL2 purging will be the responsibility of the 
Terry Fox Laboratories, Vancouver. After conditioning, the purged aliquots 
of marrow will be reinfused. In the absence of engraftment at 40 days 
(Neutrophils < 100/mm 3 ) patients will receive a 10 course of G-CSF. IfANC 
remains < 100/mm 3 , the reserve, unmanipulated marrow aliquot will be 
returned. 
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