Vaccine Responses in Patients With B Cell Malignancies

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

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

• 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:

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

• 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

• 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