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A Phase I/IIa, Dose-Ranging Safety and Efficacy Study of Topical Resiquimod for the Treatment of Early Stage Cutaneous T Cell Lymphoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Cutaneous T Cell Lymphoma

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Trial Information

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

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


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

- 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

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).

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Drug tolerability data

Outcome Description:

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.

Outcome Time Frame:

after 4 subjects have completed 4 weeks of study drug

Safety Issue:


Principal Investigator

Alain H Rook, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pennsylvania


United States: Food and Drug Administration

Study ID:




Start Date:

February 2012

Completion Date:

April 2015

Related Keywords:

  • Cutaneous T Cell Lymphoma
  • Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous



University of Pennsylvania Philadelphia, Pennsylvania  19104