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

Study Overview
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Brief Summary
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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
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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).

Official Title
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Response to the HEPLISAV-B Hepatitis B Vaccine in Treatment Naive Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's -Tyrosine Kinase Inhibitor (BTK-I)

Conditions
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Hepatitis, Safety and Tolerability

Intervention / Treatment
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* Biological: HEPLISAV-B


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve<br>Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive 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. | Biological: HEPLISAV-B<br>* 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.<br>|
| Experimental: Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib<br>Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive 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. | Biological: HEPLISAV-B<br>* 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.<br>|
| Experimental: Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib<br>Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive 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. | Biological: HEPLISAV-B<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL) | Determine the rate of hepatitis B seroprotective titer achievement (anti-HBs 10mIU/mL) following completion of the HEPLISAV-B 2-dose vaccine series (6 months after the first vaccine administration) among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib). | 6 months after the first vaccine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients | Determine the safety of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib). | 6 months after the first vaccine administration | 
| Number of Participants That Did Not Complete Study Due to Intolerance of the HEPLISAV-B Vaccine Among CLL Patients. | Determine the tolerability of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib). | 6 months after the first vaccine administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ibrutinib, Acalabrutinib, Immunology