Evaluation of Lenalidomide (REVLIMID®) to Treat Subjects With Cutaneous Lupus Erythematosus (CLE)

Cutaneous lupus erythematosus (CLE) is a chronic and often disabling disease which affects
the skin. Many patients experience scarring and inflammation of the skin, which often occur
on the face. Moderate to severe CLE is most frequently treated with antimalarial drugs such
as hydroxychloroquine, quinacrine or chloroquine. Up to 70% of CLE patients treated with
antimalarials experience a beneficial clinical response, while the remainder of patients show
no response or continue to experience progression of the disease. Thalidomide has been used
successfully in such patients, with up to 75% clinical response rate in refractory CLE
patients. However, thalidomide is a known teratogen and can cause severe birth defects,
including short, malformed limbs and damage to peripheral nerves in the extremities,
requiring patients to be monitored for pregnancy. In addition, up to 25% of patients on
thalidomide develop peripheral neuropathy. A new drug, lenalidomide (REVLIMID®), an analogue
of thalidomide, has been developed to treat neoplastic and inflammatory conditions, including
various oncologic conditions such as multiple myeloma, myelodysplastic syndrome and solid
tumors. Unlike thalidomide, lenalidomide (REVLIMID®) is not known to cause the extent of
serious side effects caused by thalidomide; however, it must also be monitored for side
effects and be distributed under the RevAssist program authorized by the drug manufacturer,
Celgene Corporation.

The primary goal of this investigator-initiated, small pilot study is to evaluate the safety
and effectiveness of lenalidomide (REVLIMID®) in CLE subjects using measurements such as the
CLASI (Cutaneous Lupus Activity and Severity Index). The study drug will be used in an
off-label indication to treat 6 subjects, for whom lenalidomide (REVLIMID®) will be provided
at no cost by the drug manufacturer. Men and women over the age of 18, who have a biopsy
proven diagnosis of refractory CLE and who have failed standard treatment with
hydroxychloroquine for up to three months, will be included in the study. Secondarily, the
study will evaluate the biologic effects of lenalidomide on pathogenic and immunologic
mechanisms of the CLE disease process during the treatment period by collecting skin
specimens (biopsies) and blood samples.

Inclusion Criteria:

- Subjects must understand and voluntarily sign Informed Consent and HIPAA forms.

- Males and females over the age of 18 at the time of signing informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements

- Subjects must have biopsy proven Cutaneous Lupus Erythematosus (CLE) either in the
form of Discoid Lupus Erythematosus (DLE) or Subacute Lupus Erythematosus (SCLE), with
or without systemic involvement.

- Subjects must have grade II erythema in at least three skin locations as defined by
the Cutaneous Lupus Activity and Severity Index (CLASI).

- Subjects must have failed standard treatment with hydroxychloroquine (Plaquenil) for
up to three months.

- Female subjects who are not pregnant.

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
within 24 hours of starting lenalidomide and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional method AT THE SAME TIME, at
least 28 days before starting to take lenalidomide (Revlimid®). FCBP must also agree
to ongoing pregnancy testing. Males must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy. All subjects must be
counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal
exposure.

- If pregnancy or a positive pregnancy test is noted in a study subject or in the
partner of a male study subject during study participation, the study drug must be
discontinued immediately.

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Female subjects who are pregnant, plan to be pregnant during the study, or who are
breastfeeding.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk for study participation, or confounds the ability to
interpret data from the study.

- Use of any other experimental drug or therapy within 28 days of baseline.

- Known hypersensitivity to thalidomide.

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

- Prior history of deep vein thrombosis (DVT).

- Prior history of pulmonary embolus (PE).

- Known positive for HIV viral DNA by qPCR.

- Positive hepatitis B surface antigen, or hepatitis C.

- Platelet count < 50,000/mcL.

- Absolute neutrophil count < 750/mcL

- Lymphopenia < 500/mcL.

- Have current signs or symptoms of severe progressive or uncontrolled renal disease
(creatinine ≥1.5 x ULN).

- If female, unwillingness to use one highly effective method and one additional method
of birth control.

- If male, unwillingness to use a latex condom during intercourse with females of
childbearing potential.

- Continued therapy with thalidomide.