A Phase II Open-Label Study Of Recombinant Human Interleukin-12 (NSC 672423) In Mycosis Fungoides (MF) Patients With Cross-Over To Phase I Evaluation Of Escalating Doses Of Interleukin-2 (NSC 373364) Administered With Interleukin-12
I. Determine the response rate (complete and partial) in patients with mycosis fungoides
treated with interleukin-12 (IL-12).
II. Determine the frequency of refractory disease in patients treated with this drug.
III. Determine the toxic effects of this drug in these patients. IV. Determine the
feasibility and dose-limiting toxic effects (DLT) of interleukin-2 (IL-2) when administered
with IL-12 in patients who have not shown disease progression after 12 weeks of IL-12 and in
those who have shown disease progression after 12 weeks of IL-12.
V. Determine the maximum tolerated dose and recommended dose of IL-2 when administered with
IL-12 in these patients.
VI. Determine immune and cytokine response over time in patients treated with this regimen.
VII. Determine the frequency of improved clinical response in patients treated with this
VIII. Determine the biologic correlates of response, including levels of interferon gamma
production, natural killer cell activity, infiltration of skin lesions by CD8-positive
cells, lymphocyte IL-12 receptor expression, signal transducers and activators of
transcription protein levels and IL-12 signal transduction, and induction of apoptosis in
tumor cells in the skin of patients treated with this regimen.
OUTLINE: This is an open-label, multicenter, dose-escalation study of interleukin-2 (IL-2).
Patients receive interleukin-12 (IL-12) subcutaneously (SC) twice weekly for 24 weeks.
Disease is assessed at 13 weeks. Patients who do not have progressive disease also receive
IL-2 SC 3 consecutive days a week during weeks 13-24. Patients with progressive disease at
week 13 receive IL-2 SC at a fixed dose during weeks 13-24.
Patients with responding disease after week 24 may continue to receive IL-2 and IL-12 for
another 12 weeks.
Cohorts of 3-6 patients receive escalating doses of IL-2 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. The recommended dose (RD) is the dose preceding
the MTD. Additional patients are treated at the RD.
Patients are followed at 6 months.
PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 28
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical response rate defined as the percentage of patients who achieve complete or partial response (Phase I)
Up to week 13
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
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