Vaccine Responses in Patients With B Cell Malignancies

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT05170399

Collaborator

(none)

500

Enrollment

Location

Arms

11.5

Anticipated Duration (Months)

43.4

Patients Per Site Per Month

Study Details

Study Description

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 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.

...

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: PNEUMOVAX 23 Biological: Fluarix Biological: FluLaval Biological: Pfizer-COVID-19 Vaccine Biological: Heplisav -B Biological: PREVNAR 13 Biological: Afluria Biological: Flucelvax Biological: Shingrix Biological: Fluzone	Phase 4

Detailed Description

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:

Determine vaccine titers in patients with CLL that are treatment naive, not receiving active treatment, or receiving targeted therapies
Determine whether interruption of Bruton tyrosine kinase inhibitor (BTKi) therapy around the time of vaccination improves vaccine titers in patients with CLL
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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Vaccine Responses in Patients With B Cell Malignancies

Anticipated Study Start Date :

Aug 30, 2022

Anticipated Primary Completion Date :

Aug 9, 2023

Anticipated Study Completion Date :

Aug 16, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine
Experimental: 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.	Biological: PNEUMOVAX 23 Pneumococcal Polysaccharide Vaccine (PPSV23) Biological: Fluarix Annual Influenza Vaccine Biological: FluLaval Annual Influenza Vaccine Biological: Pfizer-COVID-19 Vaccine COVID-19 Vaccine Biological: Heplisav -B Recombinant, adjuvanted Hepatitis (HepB-CpG) Biological: PREVNAR 13 Pneumococcal Conjugate Vaccine (PCV13) Biological: Afluria Annual Influenza Vaccine Biological: Flucelvax Annual Influenza Vaccine Biological: Shingrix Recombinant, adjuvanted Zoster Vaccine (RZV) Biological: Fluzone Annual Influenza Vaccine

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Patients with CLL AND one of the following:

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

Arm 2: Patients that have received prior cancer directed therapy and are currently not receiving active treatment
Arm 3: Must be receiving treatment with a BTKi. This arm is not available to patients receiving the HEPLISAV-B vaccine
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
Arm 5: Must be receiving treatment with a BCL-2 inhibitor

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

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

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:

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