Recruiting

Vaccine ResponsesVaccine Responses in Patients With B Cell Malignancies

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT05170399

Conditions

Lymphoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

AREXVY, ABRYSVO

PREVNAR 20

PNEUMOVAX 23

Heplisav -B

PREVNAR 13

Study Details

Brief summary:

Background:

People with B cell malignancies (blood cancers) often cannot mount a full immune response to infections or certain vaccines. Bruton tyrosine kinase inhibitors (BTKis), which are used to treat blood cancers, may also negatively affect a person s response to certain vaccines. Researchers want to learn more about vaccine responses in people with certain types of blood cancers. The findings may help develop better vaccine strategies for people with these cancers.

Objective:

To learn how well vaccines work in people who have certain types of blood cancers.

Eligibility:

Adults aged 18 years or older who have chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia, or certain non-Hodgkin lymphomas.

Design:

Participants will get one or more vaccines for illnesses, such as vaccines for hepatitis B, shingles, pneumonia, and respiratory syncytial virus (RSV). They may get more than 1 type of vaccine during the study. Not all participants will get all vaccines. Some vaccines require 2 doses.

Participants will give a blood sample before they get each vaccine. About 4 weeks after they finish each vaccine series, they will give another blood sample. Some vaccines require a second dose 3-6 weeks later. For vaccines that require a second dose, participants may also have study procedures at that visit. Participants may have 2 to 3 study visits per vaccine series.

Participants may receive a booster dose for some vaccines. The booster dose is optional. For this study, a booster means repeating the full vaccine series. Participants who receive a booster may have additional blood samples to measure their vaccine response.

Participants will have pregnancy tests, if needed.

Participants with CLL who receive BTKis may be assigned to either continue treatment or pause treatment around the time of vaccination.

Participants may give follow-up blood samples once a year for up to 5 years after each vaccine series. These blood samples are optional.

Participation will last for up to 5 years after each vaccine series is received.

Conditions

Lymphoma

Study ID

NCT05170399

Start date

Sep 14, 2022

Status verified date

Jul 31, 2026

Completion date

Nov 15, 2036

Anticipated

Primary completion date

Nov 15, 2036

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

INCLUSION CRITERIA:
Diagnosis of CLL, FL, MCL, MZL, NHL NOS or WM
Must fulfil one of the following criteria to be enrolled in one study arm per vaccine received:

1. Patients with CLL AND one of the following:

i. Arm 1: Must be treatment naive (no prior cancer directed therapy)

ii. Arm 2: Patients that have received prior cancer directed therapy and are currently not receiving active treatment

iii. Arm 3: Must be receiving treatment with a BTKi. This arm is not available to patients receiving the HEPLISAV-B vaccine

iv. Arm 4: Must be receiving treatment with a BTKi for >= 6 months prior to vaccination and be willing to hold their treatment for up to 7 weeks around the time of each vaccination. This arm is not available to patients who have had a prior episode of disease flare during periods of drug hold, or for patients with CLL that is actively progressing.

v. Arm 5: Must be receiving treatment with a BCL-2 inhibitor

Or
2. Patients with FL, MCL, MZL, NHL NOS or WM AND one of the following:

i. Arm 1: Must currently not be receiving active treatment (treatment na(SqrRoot) ve or previously treated)

ii. Arm 2: Must be receiving treatment with targeted therapies (e.g. BTKi, BCL-2 inhibitors, PI3K inhibitors, immunomodulatory agents, proteasome inhibitors)

If prior exposure to Hepatitis-B vaccination, must have documentation of negative serologic response
Age >= 18 years
Able to comprehend the investigational nature of the protocol and provide informed consent

EXCLUSION CRITERIA:

1. Female patients who are currently pregnant
2. History of severe allergic reaction to vaccines
3. Concomitant inherited immunodeficiency
4. 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.
5. Receive cytotoxic chemotherapy within 2 weeks prior to vaccination
6. Receive intravenous immunoglobulin (IVIG) within 2 months prior to vaccination
7. Receive anti-CD20 and/or anti-CD19 monoclonal antibody therapy within 6 months prior to vaccination
8. Receive cellular therapy (e.g. CAR-T cells) within 12 months prior to vaccination
9. History of allogeneic stem cell transplantation

Study Design

Enrollment

350 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Chronic Lymphocytic Leukemia (CLL) - Treatment with BCL-2 Inhibitor

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, PREVNAR 13, PNEUMOVAX 23, PREVNAR 20, AREXVY, ABRYSVO, and receive assessment of serologic and cellular response following completion of each vaccine series.

experimental: Chronic Lymphocytic Leukemia Not Receiving Active Treatment

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, PREVNAR 13, PNEUMOVAX 23, AREXVY, ABRYSVO and receive assessment of serologic and cellular response following completion of each vaccine series.

experimental: Chronic Lymphocytic Leukemia Treatment Break for BTKi

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, PREVNAR 13, PNEUMOVAX 23, PREVNAR 20, AREXVY, ABRYSVO and receive assessment of serologic and cellular response following completion of each vaccine series.

experimental: Chronic Lymphocytic Leukemia Treatment Naive

experimental: Chronic Lymphocytic Leukemia Treatment with BTKi

Participants may receive one or more of the following vaccine types: Shingrix, PREVNAR 13, PNEUMOVAX 23, PREVNAR 20, AREXVY, ABRYSVO and receive assessment of serologic and cellular response following completion of each vaccine series.

experimental: Other Non-Hodgkin Lymphoma and Waldenstrom Macroglobulinemia - Not receiving active treatment

experimental: Other Non-Hodgkin Lymphoma and Waldenstrom Macroglobulinemia - Treatment with Targeted Therapies

Interventions

AREXVY, ABRYSVO

Respiratory Syncytial Virus Vaccine

PREVNAR 20

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

PNEUMOVAX 23

Pneumococcal Polysaccharide Vaccine (PPSV23)

Heplisav -B

Recombinant, adjuvanted Hepatitis (HepB-CpG)

PREVNAR 13

Pneumococcal Conjugate Vaccine (PCV13)

Shingrix

Recombinant, adjuvanted Zoster Vaccine (RZV)

Primary outcome measure

Serologic response against each administered vaccine following completion of the vaccine series in each study arm [ Time Frame: 4 weeks after completing vaccine series ]

Central Contacts and Locations

Central contacts

Ingrid C Frey

(301) 402-0797 ingrid.frey@nih.gov

Adrian U Wiestner, M.D.

(301) 594-6855 wiestnera@mail.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222 ccopr@nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Aug 4, 2026

Last verified

Jul 31, 2026

Keywords

CLL
SLL
Booster
Lymphoma
Vaccines

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-08-04.