Vaccine Responses in Patients With B Cell Malignancies

Sponsor
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
Overall Status
Not yet recruiting
CT.gov ID
NCT05170399
Collaborator
(none)
270
Enrollment
1
Location
9
Arms
16.1
Anticipated Duration (Months)
16.8
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 DiseaseIntervention/TreatmentPhase
  • 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:
  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 FL that are treatment naive, or receiving targeted therapies

  4. Determine vaccine titers in patients with other NHL (MCL, MZL, NHL NOS) or WM that are treatment naive, 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 :
270 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 :
Apr 13, 2022
Anticipated Primary Completion Date :
Aug 9, 2022
Anticipated Study Completion Date :
Aug 16, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Chronic Lymphocytic Leukemia Treatment Naive

Treatment Naive

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 Therapy

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: Chronic Lymphocytic Leukemia - Treatment with B-cell lymphoma 2 (BCL-2) Inhibitor

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: 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, 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: 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, 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, 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 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: 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: Other Non-Hodgkin Lymphoma and Waldenstron Macrobulinemia - 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, 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

  1. 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:
No
  • 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:
  1. Arm 1: Must be treatment naive (no prior cancer directed therapy)
  1. Arm 2: Patients that have received prior cancer directed therapy and are currently not receiving active treatment

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

  3. 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

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

Or

  1. Patients with FL AND one of the following:
  1. Arm 1: Must be treatment naive (no prior cancer directed therapy)
  1. Arm 2: Must be receiving treatment with targeted therapies (e.g. BTKi, BCL-2 inhibitors, PI3K inhibitors, immunomodulatory agents, proteasome inhibitors)

Or

  1. Patients with MCL, MZL, NHL NOS or WM AND one of the following:
  1. Arm 1: Must be treatment naive (no prior cancer directed therapy)
  1. Arm 2: Must be receiving treatment with targeted therapies (e.g. BTKi, BCL-2 inhibitors, PI3K inhibitors, immunomodulatory agents)
  • 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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1National Institutes of Health Clinical CenterBethesdaMarylandUnited States20892

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: Christopher MT Pleyer, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT05170399
Other Study ID Numbers:
  • 10000444
  • 000444-H
First Posted:
Dec 28, 2021
Last Update Posted:
Apr 8, 2022
Last Verified:
Feb 9, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National Heart, Lung, and Blood Institute (NHLBI)
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 8, 2022