Clinical trial NCT03685708: HEPLISAV-B Hepatitis B Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's-Tyrosine Kinase Inhibitor (BTK-I)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis
Safety and Tolerability
Keywords: Ibrutinib
Acalabrutinib
Immunology
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-09-26
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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).

Eligibility criteria: * 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

Primary outcomes:
measure: Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL)
timeFrame: 6 months after the first vaccine administration
Secondary outcomes:
measure: Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients
timeFrame: 6 months after the first vaccine administration
measure: Number of Participants That Did Not Complete Study Due to Intolerance of the HEPLISAV-B Vaccine Among CLL Patients.
timeFrame: 6 months after the first vaccine administration
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Christopher MT Pleyer, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pleyer C, Ali MA, Cohen JI, Tian X, Soto S, Ahn IE, Gaglione EM, Nierman P, Marti GE, Hesdorffer C, Lotter J, Superata J, Wiestner A, Sun C. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood. 2021 Jan 14;137(2):185-189. doi: 10.1182/blood.2020008758.