HEPLISAV-B Hepatitis B Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's-Tyrosine Kinase Inhibitor (BTK-I)
Condition: Hepatitis; Safety and Tolerability
MeSH terms: Hepatitis A; Hepatitis B; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      People with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) tend to
      get infections more easily. This is because their immune systems are weakened. Hepatitis B is
      a virus that can be transmitted when body fluids from an infected person enter the body of an
      uninfected person. This virus can be dangerous for people with leukemia and lymphoma.
      HEPLISAV-B is a new hepatitis B vaccine. Researchers want to see if it can protect people
      with CLL/SLL from getting hepatitis B.

      Objective:

      To learn how HEPLISAV-B works in people who have CLL or SLL.

      Eligibility:

      Adults 18 years and older with CLL (or SLL). They must be getting no treatment for their CLL,
      or getting ibrutinib or acalabrutinib for it.

      Design:

      This study lasts 6 months from the date of first vaccination.

      Participants may be screened with:

      Physical exam

      Blood tests

      Pregnancy test

      Visit 1

      Participants will get blood drawn and the study vaccine. It will be given as an injection. If
      they get any symptoms within 7 days of the vaccine, they will write them in a diary.

      Visit 2

      After 3 months, participants will come back to the NIH to get another blood draw and the
      second vaccine dose.

      Visit 3

      Participants will return 3 months after the second vaccine dose was given. They will have
      blood drawn.
    

Detailed description: 
      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:

        1. Diagnosis of CLL

        2. Cohort 1: Treatment naive CLL or SLL patients

        3. Cohort 2: Subjects must be receiving ibrutinib monotherapy for at least 6 months prior
           to administration of the first vaccine dose

        4. Cohort 3: Subjects must be receiving acalabrutinib monotherapy for at least 6 months
           prior to administration of the first vaccine dose

        5. No known active or past hepatitis B infection

        6. No history of prior hepatitis B virus vaccination (approved or investigational)

        7. Age greater greater than or equal to 18 years.

        8. 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).
    

Intervention name(s): HEPLISAV-B
Intervention type(s): Biological
Intervention description(s): HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ibrutinib; Acalabrutinib; Immunology