(a) To investigate whether the FACC gene can be 
safely transferred to hematopoietic progenitor 
cells by retroviral mediated gene transfer. 
(b) To determine the extent of engraftment 
following autologous transplantation of transduced 
hematopoietic stem cells into FA patients without 
prior . ablation of recipient marrow'. 
1.62 Secondary Objectives: 
To investigate whether the transfer of a normal 
FACC gene into patients carrying defective FACC 
alleles will correct the cell phenotype and 
improve hematopoietic function. 
2.0 STUDY DESIGN 
2 . 1 Overview 
This is a single site, unblinded pilot study of gene 
therapy in patients diagnosed with Fanconi anemia. The 
treatment will be retroviral mediated transfer of a 
normal FACC gene into peripheral blood progenitors 
(PESO from patients with defective FACC alleles. To 
mobilize PBSC prior to harvest, G-CSF will be 
administered for 7 days. PBSC will be collected on 
days 5, 6 and 7, and cells will be processed for 
enrichment of CD34+ cells. Each time that PBSC are 
collected they will be cultured and transduced with the 
FACC retroviral vector. Transduced cells will then be 
reinfused into the patient. 
2 . 2 Number of Patients/Participatinq Sites 
Six participants will be enrolled in this study. 
2 . 3 Patient Management /Special Facilities 
Interested potential study patients will be scheduled 
for a screening evaluation to determine their 
eligibility. Participants will then be hospitalized 
for approximately 10 days every two to four months for 
approximately one year. Patients will be monitored 
daily while being treated, monthly between cycles, and 
every 3 months during follow-up (as an outpatient) . 
Patients will be reinfused with PBSC up to a total of 4 
times (4 cycles) . Monitoring will include evaluation 
for toxicity as well as response of hematopoietic 
function. Both DNA and RNA analyses will be used to 
document transfer and expression of the FACC gene. 
2 . 4 Study Duration 
Each PBSC cycle will take approximately two weeks to 
complete. Cycles will be repeated no more than every 2 
months, and there may be up to 4 cycles total. Upon 
completion of study treatment, patients will be 
followed every 3 months for the first year, every 6 
months for the next year, and yearly afterwards. 
3.0 STUDY TREATMENT 
3 . 1 Justification of Dosages 
It is estimated that the ratio of total bone marrow 
cells to stem cells is 10^:1. With this assumption, 
some 10^ stem cells will be exposed to the FACC vector 
for each patient. If the transduction efficiency is as 
low as 1%, stem cell transduction should still be 
detectable in patients. Preclinical studies imply that 
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