Recombinant DNA Advisory Committee - 2/10-11/92 
i as situations dictated. All of the subcommittees are offsprings of the parent body (RAC), 
and the final decisions about subcommittee deliberations rest with the RAC. Dr. Wivel 
emphasized that a new protocol has to be approved by the HGTS before going to the 
I RAC, but there is no text in the Points to Consider that calls for initial HGTS review for a 
major modification or amendment to an existing protocol. 
| Dr. Mclvor reemphasized his questions about the safety and efficacy of the protocol since 
it involved a new vector and a new target cell system. The RAC has not previously 
discussed gene transfer with the intent of introducing and expressing a gene in 
hematopoietic stem cells. Dr. B. Murray stated that the RAC can decide if the review 
should be conducted now or returned to the HGTS for first review. She reminded the 
RAC that later on there would be a vote on dissolving the HGTS. In that event, the 
review of the protocol would return to the RAC. Dr. Mclvor said his question was not so 
much whether the protocol should be reviewed now but if it should be submitted as an 
entirely new protocol. There is no detailed response to the Points to Consider. The RAC 
could either ask the investigators to resubmit the protocol in the proper form or discuss it 
now. Dr. Wivel concluded the discussion of this topic by stating that whether this 
proposed amendment is considered a modification to an existing protocol or a new 
protocol, the same standards of stringency will apply in the review. 
Dr. Leventhal stated that the proposed sequence of events for the protocol is unclear. 
Also, she posed several questions: (1) Do the investigators have stopping rules if toxicity is 
observed with G-CSF? (2) How many doses of G-CSF would be given and how often will 
the patients be evaluated, etc.? and (3) Will new patients be reinfused with both T 
lymphocytes and CD34 enriched cells. Dr. Culver responded to Dr. Leventhal's question 
regarding the clinical aspects of the protocol. The amended protocol would initially treat 
two patients who have already been treated in the original protocol. Patients would be 
apheresed to remove the T lymphocytes. Next, the patients would receive G-CSF 
injections with daily monitoring of complete blood counts. CD34( + ) cell numbers would 
be monitored in the peripheral blood while simultaneously growing and transducing the 
lymphocyte-selected fraction in the laboratory. This procedure would minimize the 
number of intravenous punctures and apheresis received by the patients. After the 
CD34( + ) cell number reached 1% or greater, G-CSF administration would be 
discontinued. The patients would be apheresed for one to three consecutive days and the 
gene-corrected T-cells would be re-infused. If no toxicities are observed from the infusions 
of transduced CD34(+) cells and lymphocytes, the patients would return home under 
standard protocol procedures. 
Dr. Leventhal asked why this new protocol would be conducted on the first patient since 
she responded positively to the original protocol. Dr. Culver responded that the 
investigators want to provide the patients with as broad an immunological repertoire as 
Recombinant DNA Research, Volume 15 
[327] 
