Oral Lenalidomide and Intravesical BCG for Therapy of Bladder Cancer

• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Duration of study treatment and follow-up - average of 12 months ] [ Designated as safety issue: Yes ]
  Patients will be assessed at monthly intervals (corresponding to Revlimid™ refill points for adverse events, classified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and these will be tabulated.
• Number of Participants Showing Effect of Addition of Revlimid on Cytokines [ Time Frame: Duration of study treatment and follow-up - average of 12 months ] [ Designated as safety issue: No ]
  The immunologic impact of the addition of Revlimid™ to BCG for secondary prevention of non-muscle-invasive transitional cell bladder cancer, in terms of a panel of correlative assays. The effect of addition of Revlimid on cytokines associated with generation of immune response and on cytotoxic T lymphocytes and memory phenotype lymphocytes.

• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Duration of study treatment and follow-up - average of 12 months ] [ Designated as safety issue: Yes ]
  Patients will be assessed at monthly intervals (corresponding to Revlimid™ refill points for adverse events, classified by CTCAE version 4.0, and these will be tabulated.
• Immunologic Impact of Revlimid [ Time Frame: Duration of study treatment and follow-up - average of 12 months ] [ Designated as safety issue: No ]
  The immunologic impact of the addition of Revlimid™ to BCG for secondary prevention of non-muscle-invasive transitional cell bladder cancer, in terms of a panel of correlative assays

The purposes of this study are to:

• find out whether participants' cancer returns or gets worse while they are taking lenalidomide and bacilli calmette-guerin (BCG);
• evaluate the safety and tolerability of the combination of lenalidomide and BCG;
• compare the cancer progression of participants taking lenalidomide and BCG versus participants taking only BCG

About 100 people with bladder cancer who are 18 years of age or older will be screened for this study throughout the United States. It is expected that about 70 people will take part, with 30 people at Moffitt Cancer Center.

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 bacilli calmette-guerin (BCG). BCG is approved by the FDA for use in people with bladder cancer.

• Drug: bacilli calmette-guerin (BCG)
  Participants will receive BCG instillations once per week for the first 6 weeks. At 3 months and 6 months, participants will receive BCG instillations once per week for three weeks.
  Other Name: BCG
• Drug: lenalidomide
  Participants may also receive capsules of lenalidomide 10 mg to swallow once per day for 7 months. The study doctor will tell participants if they will be taking lenalidomide.
  Other Name: Revlimid®

• Experimental: bacilli calmette-guerin
  Participants will be assigned to receive BCG or BCG and lenalidomide based on their cancer.
  Intervention: Drug: bacilli calmette-guerin (BCG)
• Experimental: bacilli calmette-guerin and lenalidomide
  Participants will be assigned to receive BCG or BCG and lenalidomide based on their cancer.
  Interventions:

  • Drug: bacilli calmette-guerin (BCG)
  • Drug: lenalidomide

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 (< Class II ) as defined by New York Heart 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