PROTOCOL SYNOPSIS 
Title : RETROVIRAL GENE TRANSFER OF THE FANCONI ANEMIA 
COMPLEMENTATION GROUP C GENE TO HEMATOPOIETIC PROGENITORS OF 
GROUP C PATIENTS 
Objective : 
► Primary Objectives 
The first objective will be to document the feasibility of 
transferring the FACC gene to hematopoietic progenitors. We 
hope to mark cells capable of long-term hematopoietic 
reconstitution. 
► Secondary Objectives 
Delivery of the FACC gene and subsequent expression of the 
gene in cells which carry mutant FACC alleles will, in 
theory, be therapeutic. We would expect gene- corrected stem 
cells to maintain a selective advantage within the 
hypoplastic FA marrow microenvironment. Clinically, this 
should translate into an improvement in peripheral blood 
counts in cytopenic patients. 
Population ; Patients with FA as defined by positive DEB or MMC 
testing and DNA analysis confirming mutations in FACC alleles 
will be candidates for this protocol. 
Sample Size ; This will be a pilot study consisting of six 
patients . 
Dosaae/Treatment ; 
1. Treatment will consist of < 4 cycles of peripheral blood 
progenitor (PBSC) transduction. PBSC harvest will be 
performed on days 5, 6, 7 following priming with G-CSF at a 
dose of lO/xg/kg/day subcutaneously for 7 days. 
2. PBSC will be enriched for CD34 surface expression by 
immunoaf f inity column purification (Cell Pro, Inc.). 
3. Enriched PBSC will be transduced with the FACC retroviral 
vector (via supernatant or stromal support) . 
4. PBSC will be reinfused into the patient. 
5. Cycle will be repeated up to 3 more cycles but no more 
frequently than every 2 months. 
Duration ; Patients who complete four cycles will be on study for 
a minimum of six months. They will be followed as outpatients 
indefinitely after completion of the protocol. 
Endpoints ; 
► Safety Endpoints -The study is designed primarily to 
determine whether CD34+ hematopoietic progenitors transduced 
with a normal FACC gene can be safely reinfused into FA(C) 
patients . 
► Efficacy Endpoints -Response criteria will include 
quantitation of percentage of mononuclear cells which can be 
transduced with the FACC retrovirus. Secondary criteria 
will include assessment of progenitor growth in MMC, changes 
in peripheral blood counts, and bone marrow cellularity. 
Investigators ; Principal investigators: Johnson Liu, M.D. and 
Neal Young, M.D. 
Recombinant DNA Research, Volume 19 
[571] 
