Vaccine Responsiveness in Patients With Chronic Lymphocytic Leukemia

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

Official Title
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Vaccine Responsiveness in Patients With Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: PCV13 vaccine and any of the FDA-approved COVID-19 vaccine products (BNT162b2, mRNA-1273, or Ad26.COV2.S) based on local availability.


Participation Criteria
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Eligibility Criteria
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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.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No active therapy<br>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.<br>* Vaccines administered per standard of care<br>|
| BTK inhibitor therapy (continued)<br>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.<br>* Vaccines administered per standard of care<br>|
| BTK inhibitor therapy (interrupted)<br>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.<br>* Vaccines administered per standard of care<br>|

What is the study measuring?
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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 |