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

NCT03685708 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 18014518-H-0145
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis; Safety and Tolerability

Keywords

Ibrutinib; Acalabrutinib; Immunology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients

  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.

  6 months after the first vaccine administration

Study Arms (3)

Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve

EXPERIMENTAL

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

Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib

EXPERIMENTAL

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

Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib

EXPERIMENTAL

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

Interventions

HEPLISAV-B BIOLOGICAL

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.

Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib; Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib; Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 33259596 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis

Interventions

Heplisav-B

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Christopher Pleyer, M.D. Principal Investigator, NIH, NHLBI
• Organization: National Institutes of Health (NIH) / The National Heart, Lung, and Blood Institute (NHLBI)

christopher.pleyer@nih.gov

510.709.6649

Study Officials

• Christopher MT Pleyer, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: December 7, 2018
• Primary Completion: December 16, 2020
• Study Completion: December 16, 2020
• Last Updated: February 8, 2022
• Results First Posted: December 15, 2021

Record last verified: 2021-06

Locations

US (1)