Anti-pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia

Phase II Comparative Study of Anti-Pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia

This phase II trial compares the effect of initial vaccination (PCV20 followed by PSV23) with yearly vaccinations of PSV23 to the standard 5 year vaccination in patients with chronic lymphocytic leukemia. At present chronic lymphocytic leukemia patients are poorly protected by anti-pneumococcal vaccination. Current vaccination schedule for chronic lymphocytic leukemia patients is based on general recommendations in immunocompromised patients (initial vaccination with PCV13 followed by one dose of PSV23 after an interval of two months, followed by revaccination at 5 years). Giving patients frequent immunization as compared to 5 year immunization may result in higher protective titers in patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Biological: Pneumococcal Polyvalent Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine

Detailed Description

PRIMARY OBJECTIVE:

I. Proportion of patients with anti-pneumococcal immunogenicity following early revaccination (1 year) at 2 years (Serotype to be measured are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A 19 F and 23F using the enzyme-linked immunosorbent assay [ELISA] method).

SECONDARY OBJECTIVES:

I. Number of patients with anti-pneumococcal immunogenicity at 5 years. II. Number of patients with local and/or general reaction at months 1, 3 as self-reported.

III. Number of pneumococcal infections.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive PCV 20 IM at week 0. Titers will be checked 4 weeks after this dose. Booster Vaccine: None. Titers will be checked at 12 weeks and then yearly for 5 years.

ARM B: Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: None. Annual titers will be checked for 5 years.

ARM C: Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: PCV23 booster vaccination dose will be administered yearly for 5 years. Pre-vaccination and post-vaccination (at 4 weeks) titers will be checked each time yearly for 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Seema A. Bhat, MD; Email: Seema.bhat@osumc.edu
      • Principal Investigator: Seema A. Bhat, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women >= 18 years of age
• Patients must have histologically identified chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as defined by the World Health Organization (WHO) classification of hematopoietic neoplasms
• Treatment naive CLL/SLL; No prior therapy for CLL/SLL, including chemotherapy and/or radiotherapy is allowed
• Estimated life expectancy of greater than 24 months

Exclusion Criteria:

• Patients with neutropenic (granulocyte [PMN]s < 500 cells/mm^3) or having received rituximab within 6 months
• Patients with fever (temperature > 38 degrees Celsius [C]) within 1 week
• Active infection, recent infection requiring systemic treatment that was completed =< 14 days before starting treatment on the study
• Patients with known human immunodeficiency virus (HIV) infection
• History of allergic reactions attributable to compounds of similar chemical or biologic composition to any component of pneumococcal vaccines
• Chemotherapy in 4 weeks or received Rituximab or similar anti CD20 monoclonal antibody for non-hematological indications within 6 months
• Received intravenous immunoglobulin (IVIG) within 3 months prior to vaccination
• History of allogenic stem cell transplantation
• Patients who have received cellular therapy (e.g. CAR-T cells) within 12 months prior to vaccination
• Patients who have previously received pneumococcal vaccine within the preceding 12 months
• Absolute lymphocyte count less than 500 cells/mm^3
• Patient with other severe immune deficiency
• Patients may not be receiving any other investigational agents
• Active malignancy from which the subject is considered by his or her physician to have a less than 5-year survival expectation
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and/or psychiatric illness/social situations that would limit compliance with study requirements
• Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration [> 14 days] of > 20 mg/day of prednisone) within 14 days of the first dose of study drug
• Because of the potential for H2-blockers to modulate antibody response to pneumococcal vaccine, patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy
• Unwilling or unable to participate in all required study evaluations and procedures
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (Standard ARM- No Booster); Patients receive PCV 20 IM at week 0. Titers will be checked 4 weeks after this dose. Booster Vaccine: None. Titers will be checked at 12 weeks and then yearly for 5 years.	Biological: Pneumococcal 20-valent Conjugate Vaccine; Given IM; Other Names: PCV 20; PCV 20 Vaccine; Prevnar 20
Experimental: Arm B (Experimental ARM-No Booster); Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: None. Annual titers will be checked for 5 years.	Biological: Pneumococcal Polyvalent Vaccine; Given IM; Other Names: Pneumovax 23; PPSV23; Pneumococcal Vaccine Polyvalent; PCV 23; Pneumococcal 23-valent Polysaccharide Vaccine; Pneumococcal Polysaccharide Vaccine; Pnu-Imune 23; PPSV; PPSV23 Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine; Given IM; Other Names: PCV 20; PCV 20 Vaccine; Prevnar 20
Experimental: Arm C (Experimental ARM-Annual Booster); Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: PCV23 booster vaccination dose will be administered yearly for 5 years. Pre-vaccination and post-vaccination (at 4 weeks) titers will be checked each time yearly for 5 years.	Biological: Pneumococcal Polyvalent Vaccine; Given IM; Other Names: Pneumovax 23; PPSV23; Pneumococcal Vaccine Polyvalent; PCV 23; Pneumococcal 23-valent Polysaccharide Vaccine; Pneumococcal Polysaccharide Vaccine; Pnu-Imune 23; PPSV; PPSV23 Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine; Given IM; Other Names: PCV 20; PCV 20 Vaccine; Prevnar 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with anti-pneumococcal immunogenicity following early revaccination (1 year)	Serotype to be measured are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A 19 F and 23F using the enzyme-linked immunosorbent assay (ELISA) method.	At 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with anti-pneumococcal immunogenicity	At 5 years
Proportion of patients with local and/or general reaction	At 1 and 3 months
Number of pneumococcal infections	At 5 years

Collaborators and Investigators

• Sponsor: Seema Bhat
• Investigators: Principal Investigator: Seema A Bhat, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: June 9, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: OSU-21289; NCI-2022-01763 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No