Investigation of the Enhancement of Response to Hepatitis B Vaccine by Lenalidomide in Plasma Cell Dyscrasias

The primary object of this study is to evaluate the effect of CC-5013 on the response to hepatitis B vaccine in myeloma. Secondary objectives include the evaluation of immunologic and functional genomic changes following CC-55013.

This study will be a two-center, randomized, double-blinded, placebo-controlled trial. A single dose of Hepatitis B vaccine will be administered to subjects. CC-5013 or placebo will be administered for 7 days prior to and 7 days after the vaccine. Collection of samples for immune analysis will be performed prior to the initiation of CC-5013 administration, at the time of vaccination, and 7, 14, and 28 days after vaccination. Safety assessment will be performed at each visit.

Primary Endpoint

• Titer of antibodies to hepatitis B virus Secondary Endpoints
• Immune analysis
• Hepatitis B related T cell response
• Safety profile

All the patients should not have a prior response against hepatitis B surface antigen. The study will be comprised of 64 multiple myeloma patients who have not taken any therapeutic agents in the 30 days prior to enrollment in the study. Subjects will be randomly assigned to receive or not receive CC-5013, and all will be vaccinated. The study is designed to detect a biological difference of 50% with an alpha of 0.05 and a beta of 0.8.

Inclusion criteria

• Understand and voluntarily sign an informed consent form.
• Age > = 18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Must have confirmed diagnosis of plasma cell disorder.
• Patients with prior thalidomide or CC-5013 (lenalidomide) use are eligible but these agents must have been discontinued at least 4 weeks prior to treatment in this study.
• All previous cancer therapy, including chemotherapy, and dexamethsone must have been discontinued at least 4 weeks prior to treatment in this study. Patients with recent radiation, hormonal therapy and surgery are eligible.
• Patients must not have received prior Hepatitis B vaccination.
• Patient should be negative for antibody against HbSAg.
• ANC >= 1000, Platelets >= 75,000.
• Women of childbearing potential (WCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active WCBP must agree to use two of the following adequate forms of contraception throughout the entire study (tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner). A WCBP must agree to have pregnancy tests 4 weeks after her last dose of lenalidomide. Due to the short duration of drug therapy, abstinence would also be a reasonable option.

Exclusion criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females.
• Any condition, including the presence of laboratory abnormalities, which places the subject 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.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Concurrent use of other anti-cancer agents or treatments.
• Known HIV, HBV and HCV positivity.
• Clinically significant autoimmune disease.
• Serious intercurrent illness such as active infection requiring IV antibiotics, significant cardiac or pulmonary disease.
• Psychiatric disorder, alcohol or illicit drug use.