GTI0101 (04/08/93) 
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2.0 STUDY DESIGN 
2.1 Overview 
This will be a Phase I, two-center study. Participants will at least 18 years of age with 
a diagnosis of Gaucher disease. Two sources of hematopoietic stem cells will be used, 
bone marrow or growth-factor mobilized peripheral blood stem cells (PBSC). Marrow 
harvest will be followed by enrichment of the CD34+ subpopulation. For PBSC 
harvest, G-CSF will be given for 7 days and the patient observed closely for adverse 
reactions. PBSC will be collected on days 5, 6 and 7 and cells will be processed for 
enrichment of CD34 + cells. Each time cells (marrow or PBSC) are collected they will 
be cultured and subsequently transduced with the GC-cDNA containing retroviral 
vector(s). These transduced cells will be reinfused into the patient. 
2.2 Number of Patients/Patient Management 
Ten participants will be enrolled into this study. 
Patients receiving PBSC infusions will need to be hospitalized approximately 10 days (or 
be seen daily for several hours) every two to four months for approximately one year. 
Patients will be monitored daily while being treated, and monthly between cycles and 
every 3 months during follow-up (as an out-patient). Patients will be reinfused up to a 
total of 4 times (4 cycles). As patients are not expected to develop significant therapeutic 
effects from the gene transfer, the monitoring will emphasize toxicities. Efficacy will 
be evaluated by monitoring for the presence of gene transfer into hematopoietic cells. 
Expression of the gene product will be monitored by RNA analyses to detect the presence 
of mRNA from the transferred cDNA sequence. Protein expression will be monitored 
by glucocerebrosidase enzyme activity. If the patients are on enzyme replacement 
therapy the routine monitoring for this treatment will overlap with additional tests related 
to the gene transfer aspects. 
For patients receiving the single bone marrow infusion, hospitalization periods will be 
about three days for marrow harvest and one to two days for cell infusion. Cell infusion 
may alternatively be given on an outpatient basis. Patient follow-up will be the same as 
for patients receiving PBSC infusions. 
2.3 Source of Patients/Participating sites 
This study will be conducted at NIH and CHLA. Consecutive potentially eligible 
participants will be evaluated to reduce selection bias. Both men and women will be 
eligible to participate in this study. 
2.4 Study Duration 
The bone marrow harvest and infusion will occur in less than one week. Each PBSC 
cycle will take approximately two weeks to complete. PBSC patients will be asked to 
have these cycles repeated no more than every 2 months and there may be 4 cycles total. 
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Recombinant DNA Research, Volume 17 
