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 0.03% applied as described for Treatment Group 1. However, initial applications will be 5 times per week 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.
For a given subject the concentration assignment (0.06% or 0.03%) 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 in the 0.06% dosing group and no ,more than 5 target lesions in the 0.03% treatment group 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 discretion.
Subjects in both treatment groups who experience a partial response but not a complete response at week 24 can continue treatment for up to another 12 weeks with the same concentration.
During this time they will be evaluated every 4 weeks up to 12 weeks. At that time they will have a 4 week rest period and then a final evaluation will be performed.
