Vaccine Responsiveness in Patients With Chronic Lymphocytic Leukemia

Completed

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

• Registration Number: NCT05007860
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-16
• Primary Completion: 2021-06-30
• Study First Submitted: 2021-08-09
• Study First Submitted QC: 2021-08-09
• Study First Posted: 2021-08-17
• Study Completion: 2023-06-30
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-05
• Last Update Posted: 2023-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
BTK inhibitor therapy (continued)	PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.	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.
No active therapy	PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.	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.
BTK inhibitor therapy (interrupted)	PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.	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.

Primary Outcome Measures

Name	Time	Method
Effective immune response (EIR) to PCV13 vaccination	35 days (+/- 14 days) after 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.
Effective immune response (EIR) to COVID19 vaccination	35 days (+/- 14 days) after 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.

Trial Locations

Locations (1)

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States