Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors

Study Overview
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Brief Summary
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The primary objective of the study is to assess the capability of a patient with Chronic Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) to generate an immune response to the Shingrix vaccine under first-line BTK inhibitors.

Detailed Description
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Chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM) are known risk factors for zoster reactivation, commonly called shingles. Although a recently FDA-approved recombinant, adjuvanted herpes zoster vaccine (Shingrix) is currently being offered to these populations, no study has specifically evaluated them. The purpose of the study is to complete a single-arm trial evaluating if patients with CLL or WM, while on treatment with first-line BTK inhibitors, can achieve immunologic response to Shingrix. If effective, this will result in a new, well-tolerated shingles prevention strategy for these patients. The primary objective is to assess the capability to mount a humoral immune response to Shingrix in patients with CLL or WM under first-line BTK inhibitors.

Official Title
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Serologic Response to a New Recombinant, Adjuvanted Herpes Zoster Vaccine in Patients With Chronic Lymphocytic Leukemia and Waldenström Macroglobulinemia Treated With First-Line BTK Inhibitors - A Pilot Study

Conditions
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Chronic Lymphocytic Leukemia (CLL), Waldenstrom Macroglobulinemia (WM)

Intervention / Treatment
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* Drug: Shingrix vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: They are at least 50 years of age; Have been diagnosed with chronic lymphocytic leukemia (CLL) OR Waldenström's macroglobulinemia (WM) Have been on first-line BTK inhibitor (ie ibrutinib or acalabrutinib) for at least 3 months, Prior treatment with single agent rituximab is permitted if last dose was administered over one year ago; Have at least a one-year life expectancy; Have a history of varicella (chicken-pox) OR lived in the US or any endemic country for > 30 years. Prior radiation therapy is allowed Exclusion Criteria: They have a known hypersensitivity to a vaccine component; Had herpes zoster reactivation within the past year; Had received or were scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days post-second dose; Had received or were scheduled to receive an inactivated vaccine in the period ranging from 7 days prior to Dose 1 through 7 days post- second dose; Are unable to give informed consent; Have absolute lymphocyte counts greater than 20,000 X 109/L; Are receiving treatment for CLL or WM with an additional agent other than a BTK inhibitor; Had rituximab treatment within a year prior to study start; Had prior chemotherapy.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shingrix shingles vaccine treatment<br>On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose. | Drug: Shingrix vaccine<br>* On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.<br>* Other names: Herpes Zoster Vaccine Recombinant, Adjuvanted;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A four-fold increase from baseline in serum immunoglobulin geometric mean titer to the gE viral antigen determined by enzyme linked immunosorbent assay (ELISA) at 4 weeks after vaccination. | Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects | 4 weeks following vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with humoral immunity at 4 weeks after vaccination | Blood draws performed to measure persistence of measurable anti-gE and cellular-mediated immunity; cellular-mediated response will be determined by measuring PMBC activation (by ELISPOT or flow cytometry) following stimulation with varicella glycoprotein E peptide. PBMC activation at 4 weeks and 1 year post dose will be compared to pre-vaccination activation levels. | 4 weeks following vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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shingles vaccine (Shingrix), Chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM), Pilot Study