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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia (CLL); Waldenstrom Macroglobulinemia (WM)
• Intervention / Treatment: Drug: Shingrix vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14623
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Shingrix shingles vaccine treatment; On day one, patients will receive the first of two doses of the Shingrix vaccine 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; On day one, patients will receive the first of two doses of the Shingrix vaccine 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.; Other Names: Herpes Zoster Vaccine Recombinant, Adjuvanted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration	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 the second vaccination, at approximately 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cellular Response to Vaccination 4 Weeks After the Second Vaccine Administration	Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 4 weeks after the second vaccine administration.	4 weeks following the second vaccination, at approximately 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Humoral Response to Vaccination 2 Years After the Second Vaccine Administration	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	2 years following second vaccination, approximately 26 months from day 1
Number of Participants With Cellular Response to Vaccination 2 Years After the Second Vaccine Administration	Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 2 years after the second vaccine administration.	2 years following second vaccination, approximately 26 months from day 1

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Jonathan Friedberg, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): August 3, 2022

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Chronic lymphocytic leukemia (CLL); Pilot Study; shingles vaccine (Shingrix); Waldenstrom macroglobulinemia (WM)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, B-Cell; Chronic Disease; Leukemia; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 00003112

Drug and device information, study documents

• 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