Vaccine Responsiveness in Patients With Chronic Lymphocytic Leukemia

Assessment of SARS-CoV2 (mRNA and adenovirus-based vaccines) and Conjugated Pneumococcal (PCV13) in Patients with Chronic Lymphocytic Leukemia

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Intervention / Treatment: Biological: PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with CLL/SLL receiving PCV13 +/- COVID19 vaccination.

Description

Inclusion/Exclusion Criteria:

• Age >18 years.
• Diagnosis of CLL or SLL according to WHO criteria.

• For patients receiving BTK inhibitor (Cohorts 1 and 2):

  • Patient must have no history of cytotoxic chemotherapy within 1 year (no prior history of bendamustine or fludarabine is permitted) and no history of CD20 monoclonal antibody within 6 months.
  • Patient must have no known clinical or radiographic evidence of CLL progression.

• For patients not on active therapy (Cohort 3):

  • Patient must have no history of cytotoxic chemotherapy within 1 year (no prior history of bendamustine or fludarabine is permitted) and no history of CD20 monoclonal antibody within 6 months.
  • The treating investigator must have no intention to initiate CLL therapy within 2 months.
• Patients must have not received PCV13 within 2 years. For patients with PCV13 within 5 years, S. pneumonia IgG antibody concentrations must be less than the reference value for at least 50% of S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A,19F and 23F. Patients can have received prior PPV23 within any time frame.
• Patient must have no known history of HIV or primary immune deficiency disorder, nor be taking a concurrent immune suppressing medication (e.g. steroids, methotrexate, etc.).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No active therapy; Age ≥18 years and CLL/SLL (WHO criteria). We excluded patients with known HIV or primary immune deficiency disorder, known active progression of CLL/SLL, active therapy, treating physician intent to initiate CLL/SLL therapy within ≤2 months, prior cytotoxic chemotherapy within ≤1 year, CD20 monoclonal Ab within ≤6 months, or any prior bendamustine or fludarabine. We excluded patients who received PCV13 within ≤2 years, or within 2-5 years with nonprotective titers for ≥50% of PCV13-specific S. pneumonia IgG titers.	Biological: PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.; Vaccines administered per standard of care
BTK inhibitor therapy (continued); Age ≥18 years, CLL/SLL (WHO criteria), and active therapy with a BTK inhibitor which is continued through vaccination. We excluded patients with known HIV or primary immune deficiency disorder, known active progression of CLL/SLL, prior cytotoxic chemotherapy within ≤1 year, CD20 monoclonal Ab within ≤6 months, or any prior bendamustine or fludarabine. We excluded patients who received PCV13 within ≤2 years, or within 2-5 years with nonprotective titers for ≥50% of PCV13-specific S. pneumonia IgG titers.	Biological: PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.; Vaccines administered per standard of care
BTK inhibitor therapy (interrupted); Age ≥18 years, CLL/SLL (WHO criteria), and active therapy with a BTK inhibitor which is interrupted at time of vaccination. We excluded patients with known HIV or primary immune deficiency disorder, known active progression of CLL/SLL, prior cytotoxic chemotherapy within ≤1 year, CD20 monoclonal Ab within ≤6 months, or any prior bendamustine or fludarabine. We excluded patients who received PCV13 within ≤2 years, or within 2-5 years with nonprotective titers for ≥50% of PCV13-specific S. pneumonia IgG titers.	Biological: PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.; Vaccines administered per standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective immune response (EIR) to PCV13 vaccination	EIR is defined as a >2-fold increase or conversion from a nonprotective to a protective titer for >50% of specific S. pneumonia IgG titers (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) vs baseline.	35 days (+/- 14 days) after vaccination
Effective immune response (EIR) to COVID19 vaccination	EIR is defined as a >4-fold increase from baseline, or seroconversion defined as change from negative to within the measuring interval, for specific SARS-CoV-2 antibody titers (spike protein). For patients without pre-COVID-19 vaccination. serology, a negative post-COVID-19 vaccination nucleocapsid antibody titer will be used as a surrogate for no prior infection and in this case a post-COVID-19 vaccination spike antibody titer within the measuring interval will be interpreted as an EIR.	35 days (+/- 14 days) after vaccination

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Haydu JE, Maron JS, Redd RA, Gallagher KME, Fischinger S, Barnes JA, Hochberg EP, Johnson PC, Takvorian RW, Katsis K, Portman D, Ruiters J, Sechio S, Devlin M, Regan C, Blumenthal KG, Banerji A, Judd AD, Scorsune KJ, McGree BM, Sherburne MM, Lynch JM, Weitzman JI, Lei M, Kotton CN, Dighe AS, Maus MV, Alter G, Abramson JS, Soumerai JD. Humoral and cellular immunogenicity of SARS-CoV-2 vaccines in chronic lymphocytic leukemia: a prospective cohort study. Blood Adv. 2022 Mar 22;6(6):1671-1683. doi: 10.1182/bloodadvances.2021006627.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 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
• Other Study ID Numbers: 20-296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data collected for the study, including individual deidentified participant data and a data dictionary defining each field in the set, will be made available at study closeout.
• IPD Sharing Time Frame: Data will become available at study closeout and for 5 years.
• IPD Sharing Access Criteria: Request to Principal Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

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