Oral Lenalidomide and Intravesical BCG for Therapy of Bladder Cancer

Investigators planned to screen approximately 100 people with bladder cancer who are 18 years
of age or older throughout the United States for this study.

This is a multi-center study combining two marketed drugs, one of which has not been used
previously in people with transitional cell cancer. Lenalidomide (Revlimid®) is a drug that
alters the immune system and it may also interfere with the development of tiny blood vessels
that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of
cancer cells. Lenalidomide is approved by the U.S. Food and Drug Administration (FDA) for the
treatment of specific types of myelodysplastic syndrome (MDS) and in combination with
dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior
therapy. MDS and MM are cancers of the blood. Lenalidomide is currently being tested in a
variety of cancer conditions. It is not approved by the FDA for use in people with bladder
cancer, so in this case it is considered experimental.

The other drug used in this study is Bacille Calmette-Guerrin (BCG). BCG is approved by the
FDA for use in people with bladder cancer.

Inclusion Criteria - Either control group or combination treatment:

- Understand and voluntarily sign an informed consent form

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

- Ta high grade, T1 high grade or Tis transitional cell bladder cancer, s/p
transurethral resection of bladder tumor (TURBT) with no remaining resectable disease

- Adequate cardio-pulmonary function ( Association Classification, at the time of screening, and no history of myocardial
infarction or heart failure within 6 months of start

- Laboratory test results within these ranges:

- Absolute neutrophil count ≥ 1500/mm³

- Platelet count ≥ 75,000

- Serum creatinine for which computed creatinine clearance is ≥ 30 ml/min, or
directly measured creatinine clearance ≥ 30 ml/min

- Total bilirubin ≤ 1.5 mg/dL

- Aspartate transaminase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] and
Alanine transaminase (ALT) [serum glutamate pyruvic transaminase (SGPT)] ≤ 2 x
upper limit of normal (ULN)

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

Inclusion Criteria - Combination treatment:

- Prior BCG treatment for non-muscle invasive transitional cell carcinoma (TCC) last
administered < 2 years for Ta high-grade, T1 high grade, Cis, or combination thereof

- Must be registered into the mandatory RevAssist® program, and be willing and able to
comply with the requirements of RevAssist®

- 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 effective method AT THE SAME
TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to
ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact
with a FCBP even if they have had a successful vasectomy.

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to aspirin may use warfarin or low molecular weight heparin.

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the participant from providing informed consent

- Pregnant or breast feeding (lactating females must agree not to breast feed while
taking lenalidomide)

- Any condition, including the presence of laboratory abnormalities, which places the
patient at unacceptable risk if he/she were to participate in the study 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

- Known hypersensitivity to BCG or tuberculosis vaccination

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

- Any prior use of lenalidomide

- Concurrent use of other anti-cancer agents or treatments.

- Known presence of autoimmune disease or immune deficit or chronic disease such as HIV,
infectious hepatitis (type B or C), or tuberculosis

- T2+, or N1+, or M+ disease

- Ta or T1 low grade disease only

- Concurrent use of chronic oral steroids, for any indication

- Recent history of deep venous thrombosis currently receiving anticoagulation therapy,
with the clot event being in the last 6 months

- Diagnosis of any prior malignancies for the last 5 years with exception of
definitively treated basal cell, squamous cell carcinoma of the skin, or carcinoma
in-situ of the cervix or breast

- Life expectancy less than 1 year, by treating physician estimate

- Known exposure to person with active tuberculosis within 48 hours of starting
treatment