will be treated at the MTD during Period II (or at 1 x 10'*^ cells if no MTD 
was described). 
8.1.5 Eligibility for Treatment Period II 
Patients who proceed successfully through Treatment Period I in the 
absence of dose-limiting toxicity as defined above will be considered for 
Treatment Period II. Patients must still fulfill entry criteria as outlined in 
Section 4. 
8.2 Study Design 
This is a sequential, open-label, randomized, controlled. Phase I / II clinical trial to 
study the safety of 3 different doses of genetically modified T lymphocytes in the 
setting of patients with HIV infection. The study will be conducted at one center. In 
addition, the activity of genetically modified lymphocyte infusions, as determined by 
effect on immunological status, will be descriptively assessed. 
The study has two distinct Treatment Periods. During Treatment Period I, HIV positive 
patients presenting at the participating center will be randomized in a 1:3 ratio to receive 
unmodified lymphocytes (cohort 0 comparison) or genetically modified lymphocytes at 
1 of 3 sequential dosage levels (cohorts 1-3). Cohort 1 will be filled and rate of dose- 
limiting toxicity assessed prior to cohort 2 being initiated, and the same for Cohort 3. 
A minimum of 6 patients at each dose in the genetically modified group will be enrolled 
in Treatment Period I. Evaluation of the safety of each dose of lymphocyte infusions 
will be determined by assessing the aggregate rates of adverse events. Advancement to 
the next dosage cohort will occur only if the required numbers of patients do not 
experience a DLT at the current dose level (see 1 1.1.4). 
Safety of the three dose levels of lymphocytes will be determined by comparing the 
adverse event (AE) rates and changes in vital signs and laboratory values in the three 
groups to patients receiving unmodified, ex vivo expanded syngeneic lymphocytes, and 
to baseline patient status prior to any cell infusions. 
Indices of the primary disease, HIV infection, will be followed for all patients, both as 
a safety endpoint (to monitor untoward acceleration of disease) and an activity endpoint 
(ability of the transfused lymphocytes to ameliorate viral burden). These variables 
include change in CD4 count, change in p24 antigen, and change in HIV viremia. 
8.3 Sample Size Determination 
8.3.1 T reatment Period I 
Six or nine patients evaluable for safety will be studied in the dose 
escalation phase (Treatment Period I). The following table lists the 
probability of observing various unacceptable toxicides as a function of the 
true rate of occurrence in the population of HIV infected patients treated as 
per protocol (based on binomial probabilities): 
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