ytes. A total of 144patients were randomized: 44patients to placebo, 45patients to 9mcg/kg/day Ontak and 55patients to 18mcg/kg/day Ontak. Randomization for the study was carried out at 1:1:1 for the first 73patients, 4:1:4 for the next 31patients, and 1:4:4 for the remaining 40patients. The median age of patients was 59years (range 23 to 84years); 34% were ≥65years. Fifty-five percent were men and 86% were Caucasian. Sixty-seven percent had early stage disease (≤IIa). Patients had received a median of 2anti-CTCL therapies (range 0 to 6) prior to study entry. Results for objective response rate (ORR) and progression-free survival (PFS) are shown in the table below.
Table 2: Efficacy Results in Study1 a Adjusted for disease stage and changes in randomization ratios.
b Logistic regression model adjusting for disease stage and changes in randomization ratios over the course of the study; comparisons relative to placebo.
c Cox regression analysis stratified by randomization ratio and adjusted for disease stage; comparisons relative to placebo.
Efficacy Endpoint Ontak
18mcg/kg/day
(N=55) Ontak
9mcg/kg/day
(N=45) Placebo
(N=44)
ORR %a 46% 37% 15%
p-valueb p=0.002 p=0.03 --
Median Response Duration 220days 277days 81days
PFSc
Hazard ratio 0.27 0.42
(95% CI) (0.14, 0.54) (0.20, 0.86) --
p-value p=0.0002 p=0.02
14.2 Study 2: Dose eva luation Study in CTCL (StageIIb to IVa) Patients
A randomized, double-blind study was conducted to eva luate doses of 9 or 18mcg/kg/day in 71patients with recurrent or persistent, StageIb to IVa CTCL. Entry to this study required demonstration of CD25 expression on at least 20% of the cells in any relevant tumor tissue sample (skin biopsy) or circulating cells. Tumor biopsies were not eva luated for expression of other IL-2 receptor subunit components (CD122/CD132). Ontak was administered as an IV infusion daily for 5days every 3weeks. Patients received a median of 6courses of Ontak therapy (range 1 to 11). The study population had received a median of 5prior therapies (range 1 to 12) with 63% of patients entering the trial with StageIIb or more advanced stage disease. The median age of patients was 64years (range 26 to 91years); 49% were ≥65years. Fifty-two percent were men and 75% were Caucasian.
Overall, 30% (95% CI: 18-41%) of patients treated with Ontak experienced an objective tumor response (50% reduction in tumor burden which was sustained for ≥6weeks; Table3). Seven patients (10%) achieved a complete response and 14patients (20%) achieved a partial response. The overall median duration of response, measured from first day of response, was 4months with a median duration for complete response of 9months and for partial response of 4months.
Table 3: Efficacy Results in Study2 Clinical Response 9mcg/kg/day 18mcg/kg/day
Complete Response 9% (3/35) 11% (4/36)
95% Confidence Interval (2%, 23%) (3%, 26%)
Partial Response 14% (5/35) 25% (9/36)
95% Confidence Interval (9%, 30%) (12%, 42%)
Overall Response 23% (8/35) 36% (13/36)
95% Confidence Interval (10%, 40%) (21%, 54%)
16 HOW SUPPLIED/STORAGE AND HANDLING
Ontak is supplied as 150mcg/ml, sterile, frozen solution (300mcg in 2mL) in a sterile single-use vial.
NDC 62856-603-01, 6vials in a package.
Store frozen at or below -10°C (14°F).
17 PATIENT COUNSELING INFORMATION
Advise patients to report:
Fever, chills, breathing pr
