Topical Resiquimod for the Treatment of Early Stage Cutaneous T Cell Lymphoma (CTCL)

Inclusion Criteria:

1. Males or female ≥18 years of age at the time of study enrollment
2. Have a clinical diagnosis of cutaneous T cell lymphoma CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL (atypical epidermotrophic or folliculocentric T-cells). Unconfirmed diagnosis of CTCL must have a biopsy to confirm at screening
3. Have Stage IA, IB or IIA: T1 or T2 (patches or plaques) with measurable lesions.
4. Previous treatment with at least one standard therapy used to treat Stage IA, IB or IIA CTCL including but not limited to oral corticosteroids, high-potency topical corticosteroids, topical mechlorethamine, topical bexarotene, PUVA, UVB, total body electron beam radiation, biological response or oral methotrexate.
5. Have measurable skin disease with at least 1 to 4 eligible baseline target lesions with a total area >25 cm2 but <100 cm2. Eligible lesions must be below the neck and may not involve the genitalia, intertriginous areas, internally, or to frankly ulcerated or infected skin.
6. Generally healthy other than for CTCL, or with other stable diseases/conditions that are adequately controlled.
7. Willing and able to provide written informed consent.
8. Willing and able to adhere to the protocol requirements, including but not limited to study drug dosing, study drug visits, medication and treatment restrictions, and laboratory tests.
9. Willing and able to discontinue concomitant medications or treatments for CTCL during the study.
10. If a female of child bearing potential, willing to use adequate contraception (defined as double-method contraception, e.g. oral contraceptive usage by subject and condom by partner). Non-child bearing potential is defined as being at least 2 years post-menopausal or being surgically sterile.
11. Willing to abstain from therapeutic sunbathing, tanning beds, etc. for the duration of the study.

Exclusion Criteria:

1. Have a known allergy to resiquimod or any of the excipients in the study drug.
2. Stage IIB or greater CTCL.
3. Require immediate treatment for progressive CTCL.
4. Are unable to discontinue current treatment for CTCL due to risk of progression.

5. Within 8 weeks of treatment initiation (Day 0), have received treatment with:

   • Imiquimod
   • Total body electron beam radiation
   • Investigational drugs or treatments
   • PUVA

6. Within 4 weeks of treatment initiation (Day 0), have received treatment with:

   • Local radiation therapy
   • UVB therapy
   • Any topical chemotherapy
   • Photopheresis
   • Systemic retinoids, corticosteroids, immune response modifiers (other than imiquimod), interferon inducers, chemotherapeutic agents, biologic agents including interferon
   • Topical corticosteroids or retinoids

7. Within 2 weeks of treatment initiation (Day 0), have received at or adjacent to the target treatment lesions.

   • Any surgical procedures other than biopsies related to CTCL diagnosis or follow-up
   • Any topical treatment other than bland moisturizers (creams, lotions, emollients, etc).
8. Have other concurrent cutaneous conditions in the treatment area or immediately adjacent to the treatment area that would be exacerbated by resiquimod or interfere with assessments.

9. Have a grade 2 or greater laboratory abnormalities (CTCAE v4) at baseline for any of the following:

   • Hemoglobin
   • White blood cell count
   • Platelet count
   • Alanine transferase
   • Aspartate transferase
   • Creatinine
10. Have a known history of or a positive serologic test for infection with human immunodeficiency virus or human T lymphotrophic virus.
11. Are pregnant or nursing, or intending to become pregnant within the duration of the study.
12. Have any clinically significant medical conditions that are unstable, progressive, or inadequately controlled in the opinion of the investigator, that would pose a potential risk for the subject, result in poor compliance with the study requirements, or require treatment with an excluded medication or treatment during the study.
13. Have an active chemical or alcohol dependency as assessed by the investigator.
14. Have systemic collagen vascular disorder, systemic autoimmune disease, an organ transplant or diagnosis of cancer within 5 years other than CTCL (not including basal cell carcinoma, non-invasive squamous cell cancer of the skin, malignant melanoma in situ, or cervical carcinoma in situ).