Vaccine Responses in Patients With B Cell Malignancies

NCT ID: NCT05170399

Last Updated: 2025-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-14

Study Completion Date

2026-08-16

Brief Summary

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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 COVID-19, hepatitis B, and shingles. They can choose which vaccines they receive. They will give a blood sample before they get each vaccine. Some vaccines require a second dose 3-6 weeks later. Participants may give an optional blood sample with the second vaccine dose. About 4 weeks after they finish each vaccine series, they will give another blood sample. They will have 2-3 study visits per vaccine.

Participants may receive a booster dose for some vaccines. The booster dose is optional. They will give another blood sample with the booster dose.

Participants will have pregnancy tests, if needed.

Participants with CLL who receive BTKis may be asked to pause treatment for up to 7 weeks.

Participants may give follow-up blood samples up to 2 times a year for 5 years. These blood samples are optional.

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

Detailed Description

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Study Description:

This study aims to determine vaccine titers in B-cell malignancies; specifically, in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), or other non-Hodgkin lymphomas (NHL) \[follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphomas (MZLs) and indolent NHL not otherwise specified (NOS)\], or in Waldenstrom Macroglobulinemia (WM).

Note: Since CLL and SLL are considered the same disease, CLL/SLL will be referred to as CLL hereafter, unless otherwise specified.

Objectives: Primary Objective:

Determine vaccine titers following vaccination in patients with B-cell malignancies who are either receiving targeted therapies or not receiving active treatment

Secondary Objectives:

1. Determine vaccine titers in patients with CLL that are treatment naive, not receiving active treatment, or receiving targeted therapies
2. Determine whether interruption of Bruton tyrosine kinase inhibitor (BTKi) therapy around the time of vaccination improves vaccine titers in patients with CLL
3. Determine vaccine titers in patients with NHL (FL, MCL, MZL, NHL NOS) or WM that are not receiving active treatment, or receiving targeted therapies

Endpoints:

The primary efficacy endpoint will be the serologic titer against each administered vaccine following completion of the vaccine series in each study arm

Conditions

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Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Chronic Lymphocytic Leukemia Not Receiving Active Treatment

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Chronic Lymphocytic Leukemia Treatment Break for BTKi

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Chronic Lymphocytic Leukemia Treatment Naive

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Chronic Lymphocytic Leukemia Treatment with BTKi

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Follicular Lymphoma

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Follicular Lymphoma Treatment Naive

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Other Non-Hodgkin Lymphoma and Waldenstrom Macroglobulinemia

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

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

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Participants diagnosed with Chronic Lymphocytic Leukemia (CLL)

Participants may receive one or more of the following vaccine types: Shingrix, Heplisav -B, Fluzone, Afluria, Fluarix, Flucelvax, FluLaval, PREVNAR 13, PNEUMOVAX 23, Pfizer-COVID-19, Moderna-COVID-19 and receive assessment of serologic and cellular response following completion of each vaccine series.

Group Type EXPERIMENTAL

Fluzone

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Shingrix

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Zoster Vaccine (RZV)

Flucelvax

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Afluria

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PREVNAR 13

Intervention Type BIOLOGICAL

Pneumococcal Conjugate Vaccine (PCV13)

Heplisav -B

Intervention Type BIOLOGICAL

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Pfizer-COVID-19 Vaccine

Intervention Type BIOLOGICAL

COVID-19 Vaccine

FluLaval

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

Fluarix

Intervention Type BIOLOGICAL

Annual Influenza Vaccine

PNEUMOVAX 23

Intervention Type BIOLOGICAL

Pneumococcal Polysaccharide Vaccine (PPSV23)

PREVNAR 20

Intervention Type DRUG

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

AREXVY, ABRYSVO

Intervention Type DRUG

Respiratory Syncytial Virus Vaccine

Interventions

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Fluzone

Annual Influenza Vaccine

Intervention Type BIOLOGICAL

Shingrix

Recombinant, adjuvanted Zoster Vaccine (RZV)

Intervention Type BIOLOGICAL

Flucelvax

Annual Influenza Vaccine

Intervention Type BIOLOGICAL

Afluria

Annual Influenza Vaccine

Intervention Type BIOLOGICAL

PREVNAR 13

Pneumococcal Conjugate Vaccine (PCV13)

Intervention Type BIOLOGICAL

Heplisav -B

Recombinant, adjuvanted Hepatitis (HepB-CpG)

Intervention Type BIOLOGICAL

Pfizer-COVID-19 Vaccine

COVID-19 Vaccine

Intervention Type BIOLOGICAL

FluLaval

Annual Influenza Vaccine

Intervention Type BIOLOGICAL

Fluarix

Annual Influenza Vaccine

Intervention Type BIOLOGICAL

PNEUMOVAX 23

Pneumococcal Polysaccharide Vaccine (PPSV23)

Intervention Type BIOLOGICAL

PREVNAR 20

Pneumococcal 20-Valent Conjugate Vaccine (PCV20)

Intervention Type DRUG

AREXVY, ABRYSVO

Respiratory Syncytial Virus Vaccine

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian U Wiestner, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rachel A Adams

Role: CONTACT

(301) 827-1094

Adrian U Wiestner, M.D.

Role: CONTACT

(301) 594-6855

Facility Contacts

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

Role: primary

800-411-1222 ext. TTY dial 711

Related Links

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Other Identifiers

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000444-H

Identifier Type: -

Identifier Source: secondary_id

10000444

Identifier Type: -

Identifier Source: org_study_id

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