Evaluating vaccine responses in patients with blood cancers

Vaccine Responses in Patients With B Cell Malignancies

This study is testing how well different vaccines work in adults with blood cancers like chronic lymphocytic leukemia and certain lymphomas to see if treatments affect their immune response.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05170399 on ClinicalTrials.gov

What this trial studies

This study investigates how well vaccines work in adults with B cell malignancies, such as chronic lymphocytic leukemia (CLL) and certain non-Hodgkin lymphomas. Participants will receive various vaccines, including those for COVID-19 and shingles, and their immune responses will be measured through blood samples taken before vaccination. The study aims to determine vaccine titers in patients receiving targeted therapies and those not undergoing active treatment, with a focus on understanding the impact of Bruton tyrosine kinase inhibitors on vaccine efficacy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, or specific types of non-Hodgkin lymphoma.

Not a fit: Patients with active disease progression or those who have had a prior episode of disease flare during drug hold may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved vaccination strategies for patients with B cell malignancies, enhancing their immune responses to infections.

How similar studies have performed: Other studies have explored vaccine responses in immunocompromised populations, showing varying degrees of success, but this specific approach in B cell malignancies is relatively novel.

Eligibility criteria

* 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

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Adrian U Wiestner, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: Rachel A Adams

Conditions: Lymphoma, CLL, SLL, Booster, Vaccines