Vaccine Responses in Patients With B Cell Malignancies

Lymphoma Clinical Trial

Official title:

Vaccine Responses in Patients With B Cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05170399
• Other study ID #: 10000444
• Secondary ID: 000444-H
• Status: Recruiting
• Phase: Phase 4
• Start date: September 14, 2022
• Est. completion date: August 16, 2024

Study information

• Verified date: May 10, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Shellin Jose
• Phone: (301) 529-7119
• Email: shellin.jose[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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

Secondary Endpoints: N/A

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: August 16, 2024
• Est. primary completion date: August 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Lymphoma
• Neoplasms

Intervention

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

Drug:
• PREVNAR 20
Pneumococcal 20-Valent Conjugate Vaccine (PCV20)
• AREXVY, ABRYSVO
Respiratory Syncytial Virus Vaccine

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serologic response against each administered vaccine following completion of the vaccine series in each study arm	vaccine titer	4 weeks after completing vaccine series

External Links

•   NIH Clinical Center Detailed Web Page