Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T-cell Lymphoma (CTCL)

This study will evaluate a novel approach to the treatment of patches and plaques in the skin
of patients diagnosed with cutaneous t-cell lymphoma utilizing a dissolvable microneedle
array (MNA) delivery device that is used to directly and specifically deliver a drug to the
tumor microenvironment for skin cancer therapy. We will utilize MNAs to deliver a
well-characterized, potent chemotherapeutic agent (doxorubicin) to kill topically accessible,
cutaneous T-cell lymphoma cells. In addition to directly killing cancer cells, doxorubicin is
known to induce an immunologic cell death with the potential to simultaneously convert a
cutaneous neoplasm into a highly potent patient specific immunogen capable of inducing
innate, adaptive, and tumor specific effector and memory immune responses. Importantly,
doxorubicin is currently in clinical use with a well-established safety profile. It is
anticipated that use of the MNA-Doxorubicin (MNA-D) delivery system will enable direct and
specific delivery of chemotherapy to the tumor, thereby avoiding any potential for systemic
toxicity. The study will be conducted in two phases, with the first being a safety
dose-finding phase and the second phase for efficacy and safety evaluation.

Inclusion Criteria:

- Diagnosis of Cutaneous T-cell Lymphoma (CTCL) based upon a skin biopsy diagnostic of
atypical epidermotropism of folliculocentric or epidermotropic T-cells.

- Current stage of IA or IB.

- Expected survival of greater than or equal to12 months.

- Not be on any other investigational device/drug treatment.

- Have a sufficient number (i.e., n=4 for first dose cohort in Initial Safety
Evaluation; n=3 for remainder of subjects) and surface area (> 5 cm2) of CTCL patches
or plaques for Micro needle array-Doxorubicin (MNA-D) and Micro needle array (MNA)
application.

- Willing to adhere to the instructions of the Investigator and his research team and
sign an Informed Consent Form prior to entry into the study.

- Have the following initial and subsequent pretreatment laboratory parameters:
granulocytes ≥2,000/mm3; platelets >50,000/mm3; serum creatinine ≤2X the upper limit
of normal (ULN); AST, ALT, , LDH, Alk phos ≤3X the ULN.Subjects must be ³ 18 years of
age and must be able to understand the written informed consent/assent document.

- Have no evidence of active infection, regardless of the degree of severity or
localization. Subjects with active infections (whether or not they require antibiotic
therapy) may be eligible for study participation after complete resolution of the
infection. Subjects on antibiotic therapy must be off antibiotics before beginning
treatment.

- Not receive any other treatment for CTCL except emollients of subject's choice without
topical steroids, anti-fungal or antibacterial topical preparations.

- Willing to discontinue concomitant medications for CTCL for the duration of their
study participation, including: high dose topical steroids - 2 week washout; oral
steroids above 10 mg - 3 week washout; Psoralen + Ultraviolet A light (PUVA) or
ultraviolet B light (UVB) (including sunbathing, tanning beds, etc.) - 2 week washout;
extracorporeal photopheresis - 2 week washout; Electron Beam - 2 weeks washout;
chemotherapeutic agents - 3 week washout; bexarotene capsules or other oral biologics
- 2 week washout; and topical nitrogen mustard - 2 week washout.

- May re-enroll in the study if greater than 4 weeks elapses between courses and if all
other inclusion/exclusion criteria are met.

Exclusion Criteria:

- Uncontrolled pain.

- Known history of autoimmune disease; or active HIV, HTLV-1, and/or hepatitis
infection.

- Pregnant or lactating.

- Have sensitivity to drugs that provide local anesthesia.

- Have active malignancies with the exception of non-metastatic prostate cancer and
carcinoma in situ of the skin and cervix.