HepatitisPhase 2NCT03685708
HEPLISAV-B Hepatitis B Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's-Tyrosine Kinase Inhibitor (BTK-I)
A Phase 2 study testing HEPLISAV-B in people with Hepatitis and Safety and Tolerability, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hepatitis, Safety and Tolerability
- What is being tested?
- HEPLISAV-B
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2018to 16 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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)
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.
Read more
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.
Read the 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:
- 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:
- 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:
- Determine the safety and tolerability of the HEPLISAV-B vaccine among CLL patients who are treatment naive or receiving BTK-Is (ibrutinib or acalabrutinib).
- Conditions
- Hepatitis, Safety and Tolerability
- Being tested
- HEPLISAV-B
- Keywords
- Ibrutinib, Acalabrutinib, Immunology
- Medical subject headings
- Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HEPLISAV-BBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: HEPLISAV-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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).
Measured: 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).
Measured: 6 months after the first vaccine administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start7 Dec 2018
- Primary completion16 Dec 2020
- Study completion16 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HepatitisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christopher MT Pleyer, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03685708
- Sponsor's protocol ID
- 180145
- Other IDs
- 18-H-0145
- Status last verified
- Jun 2021
- First submitted
- 25 Sep 2018
- Last updated
- 8 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33259596
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03685708
- Acronym / sponsor ID
- 180145
- Conditions
- Hepatitis, Safety and Tolerability
- Keywords
- Ibrutinib, Acalabrutinib, Immunology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 7 Dec 2018 (actual)
- Primary completion
- 16 Dec 2020 (actual)
- Study completion
- 16 Dec 2020 (actual)
- First posted
- 26 Sep 2018 (actual)
- Results
- Posted 15 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- Determine the safety and tolerability of the HEPLISAV-B vaccine among CLL patients who are treatment naive or receiving BTK-Is (ibrutinib or acalabrutinib).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve | Experimental | Biological: HEPLISAV-BTreatment 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. |
| Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib | Experimental | Biological: HEPLISAV-BIbrutinib 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. |
| Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib | Experimental | Biological: HEPLISAV-BAcalabrutinib 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HEPLISAV-BHEPLISAV-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 | Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib, Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib, Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve |
Primary outcome
Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL)
Time frame: 6 months after the first vaccine administration
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).
2 secondary outcomes
Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients
Time frame: 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.
Time frame: 6 months after the first vaccine administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33259596Pleyer 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher MT Pleyer, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HEPLISAV-B in people with Hepatitis and Safety and Tolerability, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL) (time frame: 6 months after the first vaccine administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03685708, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2022.