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

Primary Purpose

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

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Shingrix vaccine
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring shingles vaccine (Shingrix), Chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM), Pilot Study

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Shingrix shingles vaccine treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
December 7, 2018
Last Updated
January 9, 2023
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT03771157
Brief Title
Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
September 1, 2020 (Actual)
Study Completion Date
August 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL), Waldenstrom Macroglobulinemia (WM)
Keywords
shingles vaccine (Shingrix), Chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM), Pilot Study

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Shingrix shingles vaccine treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Shingrix vaccine
Other Intervention Name(s)
Herpes Zoster Vaccine Recombinant, Adjuvanted
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
4 weeks following vaccination
Secondary Outcome Measure Information:
Title
Proportion of patients with humoral immunity at 4 weeks after vaccination
Description
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.
Time Frame
4 weeks following vaccination
Other Pre-specified Outcome Measures:
Title
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 2 years after vaccination.
Description
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
Time Frame
2 years following vaccination
Title
Proportion of patients with humoral immunity at 2 years after vaccination
Description
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 2 years post dose will be compared to pre-vaccination activation levels.
Time Frame
2 years following vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Friedberg, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States

12. IPD Sharing Statement

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

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