A Phase I/IIa, Dose-Ranging Safety and Efficacy Study of Topical Resiquimod for the Treatment of Early Stage Cutaneous T Cell Lymphoma
This is an open-label, dose-ranging study in subjects with early stage (IA, IB, 2A) CTCL.
Patients with early stage CTCL will be screened for eligibility. Eligible subjects will be
enrolled in up to 2 treatment groups of up to 8 subjects each.
Treatment groups will be:
1. Resiquimod 0.06% will be applied in dosing frequencies that are periodically adjusted
according to tolerability. Subjects will begin dosing at 3 times per week (3x/wk), and
will be evaluated at the clinic every two weeks. The dosing frequency (1, 2, 3, 5, or
7x/wk) may be adjusted in a stepwise manner after each two week interval based on the
physician assessment of tolerability (maintained, increased, decreased with or without
a dosing interruption [rest period]). Resiquimod will be applied for 8 weeks (COT1)
followed by a 4 week no-treatment period. If the subject has not required permanent
discontinuation from treatment, the subject will repeat a second course of treatment of
8 weeks (COT2) followed by a 4 week no-treatment period. Subjects will apply up to 500
mg of study drug per day based upon the total surface area that is treated (~250 mg of
product / 50 cm2 of lesion surface area).
2. Resiquimod 0.2% applied as described for Treatment Group 1. However, initial
applications will be once weekly due to the increased potency of this concentration
with the dosing frequency adjusted upward as tolerated every two weeks.
The initial cohort will be assigned to Treatment Group 1. After 4 subjects have completed at
least 4 weeks of dosing, a safety review meeting will be conducted by a committee consisting
of the P.I., a biostatistician, and at least one other physician familiar with CTCL
responses. The Safety Review Committee (SRC) will determine, based on the review of the
tolerability data, the starting concentration/frequency of the next group of 4 subjects.
Subsequently, the SRC will meet after each group of 4 subjects have completed at least 4
weeks of treatment to determine the starting concentration/frequency of the next group (see
protocol section 6.4 for further details). No subjects will be enrolled at the 0.2%
concentration until all 8 have been evaluated in the 0.06% group; dosing will begin in the
0.2% concentration group only if ≥ 6 of 8 subjects tolerate the 0.06% concentration at a
frequency of at least 2x/wk without a DLT (see 6.4.6). For a given subject the concentration
assignment (0.06% or 0.2%) will remain the same (only frequency may vary). It is planned
that approximately 8 subjects will be enrolled in each group.
A treatment regimen will be considered inadequately tolerated if 2 or more subjects within
the treatment cohort require protocol mandated permanent discontinuation. Treatment regimens
for newly enrolled subjects and/or of current subjects on treatment will be adjusted
accordingly per protocol. The Safety Review Committee (SRC) will determine the occurrence of
any dose-limiting toxicities (DLTs), defined below in Section 6.4.6. A subsequent phase II
study will further explore efficacy of the MTD in an expanded study.
Up to 2 subjects per Treatment Group who discontinue from the study due to reasons unrelated
to safety reasons (e.g. personal, lost to follow-up, etc) may be replaced.
The investigator will determine the target CTCL lesions and treatment area. During each COT,
subjects will treat at least 1 but no more than 4 target lesions with a total combined
treatment area that is ≥25 cm2 but ≤100 cm2. Unless a lesion is considered to have
completely resolved by clinical assessment at 4 weeks post COT1 (PCOT1), subjects will treat
the same baseline target lesions throughout the COT1 and COT2. The amount of drug applied
per dose during each COT may vary depending on the total size of the target lesions but may
not exceed 500 mg per day.
For COT1, subjects will be evaluated at baseline, Week 2, 4, 6, 8 and 12 (PCOT1). For COT2,
subjects will be evaluated at Week 12 (PCOT1/COT2 baseline) 14, 16, 18, 20 and 24 (4 weeks
post COT2, PCOT2). The End of study (EOS) will be at PCOT2, or if a subject permanently
discontinues study drug prematurely, at 4 weeks after the last dose.
Rest periods from treatment may be instituted by the investigator as needed to manage
tolerance, with resumption of treatment upon adequate resolution per investigator
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Drug tolerability data
After four subjects have completed at least four weeks of study drug dosing a safety review meeting will be conducted by a committee. The committee will determine based on the review of the tolerability data the starting concentration/frequency of the next group. No subjects will be enrolled in the higher concentration (0.2%). group until all eight have been evaluated in the lower dose (0.06%) group.
after 4 subjects have completed 4 weeks of study drug
Alain H Rook, M.D.
University of Pennsylvania
United States: Food and Drug Administration
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