Response to the SHINGRIX Varicella Zoster Virus (VZV) Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's Tyrosine Kinase Inhibitor (BTK-I)

This study aims to determine the efficacy of the SHINGRIX varicella zoster virus (VZV) vaccine in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients that are treatment naive or receiving Bruton s-tyrosine kinase inhibitor (BTK-I). (Note: Since CLL and SLL are considered the same disease, CLL/SLL will be referred to as CLL hereafter, unless otherwise specified).

Key Eligibility Criteria:

• Diagnosis of CLL or SLL
• Cohort 1: Treatment naive CLL or SLL patients
• Cohort 2: Subjects must be receiving ibrutinib for at least 6 months prior to administration of the first vaccine dose
• Cohort 3: Subjects must be receiving acalabrutinib for at least 6 months prior to administration of the first vaccine dose
• Age greater than or equal to 18 years
• ECOG performance status of 0-1

Design:

Patients with CLL will enroll on the study for the purpose of determining the SHINGRIX vaccine efficacy in patients who are treatment naive or receiving BTK-I therapy. A series of 2 doses of SHINGRIX will be given at 0- and 3- month schedule by intramuscular injection. Subjects will be followed for 6 months and receive assessment of serologic response 6 months after the first vaccine dose administration.

Study Objectives:

Primary Objective:

a)Determine the serologic response against VZV after completing the SHINGRIX (RZV) 2-

dose vaccine series in the following populations:

• CLL patients that are treatment naive (n=54)
• CLL patients receiving treatment with ibrutinib (n=27)
• CLL patients receiving treatment with acalabrutinib (n=27)

Secondary Objective:

a) Determine the safety and tolerability of the SHINGRIX vaccine among CLL patients who are treatment naive or receiving BTK-Is (ibrutinib or acalabrutinib).

• INCLUSION CRITERIA:
• Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group
• Cohort 1:Treatment naive CLL/SLL patients
• Cohort 2: Subjects must be receiving treatment ibrutinib for at least 6 months prior to administration of the first vaccine dose
• Cohort 3: Subjects must be receiving acalabrutinib for at least 6 months prior to administration of the first vaccine dose
• No active, symptomatic VZV or herpes zoster infection within 12 months prior to vaccination
• No exposure to the live VZV vaccine (ZOSTAVAX) within 12 months prior to vaccination
• No prior exposure to the SHINGRIX vaccine
• Age greater than or equal to 18 years.
• ECOG performance status of 0-2
• Able to comprehend the investigational nature of the protocol and provide informed consent

Exclusion criteria

• Female patients who are currently in pregnancy
• Any uncontrolled active systemic infection
• 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
• Severe allergic reaction to any component of SHINGRIX.
• Received intravenous immunoglobulin (IVIG) within 3 months prior to vaccination.
• Concomitant use of immunosuppressive agents (e.g. steroids, radio

therapy, chemotherapy)

• Hereditary or acquired immunodeficiency syndrome unrelated to chronic lymphocytic leukemia
• Non-English speaking individuals will be excluded from the study