Clinical trial NCT03702231: 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)
Official title: Response to the SHINGRIX Varicella Zoster Virus (VZV) Vaccine in Chronic Lymphocytic Leukemia (CLL) Patients That Are Treatment Naive or Receiving Bruton s-Tyrosine Kinase Inhibitor (BTK-I) Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Safety and Tolerability
Compare SHINGRIX Vaccine Response Rates
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: Ibrutinib
Acalabrutinib
Shingles
Herpes
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-10-11
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Background:

People who have cancer tend to get sick more often. This is in part because of the cancer treatments they get. Because of this, they may get shingles. Scientists had thought people with chronic lymphocytic leukemia (CLL) should not get the shingles vaccine. Now there is a new shingles vaccine that is not live and cannot cause shingles. The new shingles vaccine may protect people with weak immune systems from getting shingles. This is currently shown to be safe to give people 50 years and older to prevent shingles. Researchers want to test how safe the vaccine is and how it works in people with CLL.

Objective:

To learn how a new shingles vaccine works in people who have chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL).

Eligibility:

Adults ages 18 years and older with CLL or SLL who are not being treated for CLL or who are getting certain treatments.

Design:

Participants will be screened with a chart review or through another protocol.

Visit 1

At visit 1, participants may have a pregnancy test, blood test, or physical exam.

Pregnant participants cannot be in the study.

Eligible participants will get the shingles vaccine as an injection.

Participants will receive a diary and write down any symptoms they have for 7 days after the vaccines.

Visit 2

Visit 2 will be 3 months later. Participants will have blood taken and get another dose of the vaccine.

Participants will receive a diary and write down any symptoms they have for 7 days after the vaccines.

Visit 3

Visit 3 will be 3 months after visit 2. Participants will have blood taken.

Participants may be able to get an additional vaccine the same day as the shingles vaccine.

Detailed description: 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).

Eligibility criteria: * 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

Primary outcomes:
measure: Number of Participants With Varicella Zoster Virus (VZV) Seroprotective Titer
timeFrame: 6 months after the first vaccine administration
Secondary outcomes:
measure: Number of Participants That Experienced Serious Adverse Events Following the SHINGRIX Vaccine Among Chronic Lymphocytic Leukemia Patients.
timeFrame: 6 months after the first vaccine administration
measure: Number of Participants That Did Not Complete Study Due to Intolerance of the SHINGRIX Vaccine Among Chronic Lymphocytic Leukemia Patients.
timeFrame: 6 months after the first vaccine administration
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Christopher MT Pleyer, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pleyer C, Laing KJ, Ali MA, McClurkan CL, Soto S, Ahn IE, Nierman P, Maddux E, Lotter J, Superata J, Tian X, Wiestner A, Cohen JI, Koelle DM, Sun C. BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL. Blood Adv. 2022 Mar 22;6(6):1732-1740. doi: 10.1182/bloodadvances.2021006574.
citation: Pleyer C, Ali MA, Cohen JI, Tian X, Soto S, Ahn IE, Gaglione EM, Nierman P, Marti GE, Hesdorffer C, Lotter J, Superata J, Wiestner A, Sun C. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood. 2021 Jan 14;137(2):185-189. doi: 10.1182/blood.2020008758.