HEPLISAV-B Hepatitis B Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's-Tyrosine Kinase Inhibitor (BTK-I)

This study aims to determine the HEPLISAV-B hepatitis B vaccine efficacy in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) lymphocytic patients that are treatment naive or receiving Bruton s-tyrosine kinase inhibitor (BTK-I) therapy. (Note: Since CLL and SLL are considered the same disease, CLL/SLL will be referred to as CLL hereafter, unless otherwise specified).

Key Eligibility Criteria:

• Diagnosis of CLL
• Cohort 1: Treatment naive CLL or SLL patients
• Cohort 2: Subjects must be receiving ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose
• Cohort 3: Subjects must be receiving acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose
• No known active or past hepatitis B infection
• No history of prior hepatitis B virus vaccination (approved or investigational)
• Age greater greater than or equal to 18 years.
• ECOG performance status of 0-1

Design:

Patients with CLL will enroll on the study for the purpose of determining the HEPLISAV-B vaccine efficacy in patients who are treatment naive ore receiving BTK-I therapy. A series of 2 doses of HEPLISAV-B will be given on a 0- and 3- month schedule by intramuscular injection. Subjects will be followed at regular intervals and receive serologic response assessment following completion of the HEPLISAV-B vaccine series (6 months after the first vaccine

administration).

Study Objectives:

Primary Objective:

a) Determine the rate of hepatitis B seroprotective titer achievement (anti-HBs greater than or equal to 10mIU/mL) following completion of the HEPLISAV-B 2-dose vaccine series (6 months after the first vaccine administration) in the following populations:

• CLL patients who are treatment naive (n=54)
• CLL patients receiving treatment with ibrutinib (n=27)
• CLL patients receiving treatment with acalabrutinib (n=27)

Secondary Objective:

a) Determine the safety and tolerability of the HEPLISAV-B vaccine among CLL patients who are treatment naive or receiving BTK-Is (ibrutinib or acalabrutinib).

• INCLUSION CRITERIA:
• Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group.
• No known active or past hepatitis B infection
• No history of prior hepatitis B virus vaccination (approved or investigational)
• History of negative hepatitis B viral titers (negative HBsAg, HBsAb and HBcAb)
• Cohort 1: Treatment naive CLL patients
• Cohort 2: Subjects must be receiving ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose
• Cohort 3: Subjects must be receiving acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose
• Age greater than or equal to 18 years.
• ECOG performance status of 0-1
• Able to comprehend the investigational nature of the protocol and provide informed consent.

Exclusion criteria

• Female patients who are currently pregnant.
• Any uncontrolled active systemic infection
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk
• History of severe allergic reaction to any component of HEPLISAV-B, including yeast
• Receive intravenous or subcutaneous immunoglobulin (IVIG) within 3 months prior to vaccination
• Concomitant use of immunosuppressive agents (e.g. steroids, radiotherapy, chemotherapy)
• Hereditary or acquired immunodeficiency syndrome unrelated to CLL
• Non-English speaking individuals will be excluded from the study