Pneumococcal Vaccination for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Seema A. Bhat

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Seema Bhat

Must not be taking: H2-blockers, Immunosuppressants

Disqualifiers: HIV, Active infection, Stem cell transplant, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking H2-blockers (medications like cimetidine or ranitidine) before starting the study. If you are on systemic immunosuppressant therapy, you must stop it at least 14 days before the first dose of the study drug.

What data supports the effectiveness of the pneumococcal vaccination treatment for patients with chronic lymphocytic leukemia?

Research shows that the 13-valent pneumococcal conjugate vaccine (PCV13) triggers a better immune response than the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with chronic lymphocytic leukemia (CLL). However, the overall serologic response to vaccination in CLL patients is low, with only a small percentage achieving protective antibody levels.

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Is the pneumococcal vaccine safe for people with chronic lymphocytic leukemia?

The pneumococcal vaccines, including the 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23), have been recommended for people with chronic lymphocytic leukemia (CLL) to prevent infections. While these vaccines are generally considered safe, the immune response in CLL patients may be lower compared to healthy individuals.

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How does the pneumococcal vaccination treatment for chronic lymphocytic leukemia differ from other treatments?

The pneumococcal vaccination treatment for chronic lymphocytic leukemia is unique because it involves a combination of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23), which are specifically recommended to prevent pneumococcal infections in these patients. This approach is tailored to address the increased risk of infections due to immune system dysfunction in CLL patients, and the conjugate vaccine (PCV13) is noted to trigger a better immune response compared to the polysaccharide vaccine (PPSV23) alone.

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Eligibility Criteria

Adults diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma who haven't had previous treatments can join. They should have a life expectancy over 24 months, not be on certain immune system drugs, and must understand the study to give consent. Those with recent chemotherapy, vaccinations, very low lymphocyte counts, severe immune deficiencies, HIV infection or other serious illnesses cannot participate.

Inclusion Criteria

I have never received treatment for my CLL/SLL.

I am 18 years old or older.

I have been diagnosed with CLL or SLL according to WHO standards.

Exclusion Criteria

I have not had cellular therapy like CAR-T in the last 12 months.

I will stop taking H2-blockers before starting the treatment.

I have not had a fever over 38°C in the past week.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Vaccination

Participants receive PCV20 IM at week 0. In Arm B and C, PSV23 IM is administered at week 8.

12 weeks

3 visits (in-person)

Follow-up

Participants' titers are checked annually for 5 years to monitor immunogenicity.

5 years

Annual visits (in-person)

Booster Vaccination (Arm C only)

Participants in Arm C receive a PCV23 booster vaccination dose yearly for 5 years.

5 years

Annual visits (in-person)

Participant Groups

The trial is testing two anti-pneumococcal vaccine schedules in patients with chronic lymphocytic leukemia: one involves initial vaccination followed by yearly shots; the other uses the standard five-year schedule. The goal is to see if more frequent vaccines offer better protection against pneumonia.

Group I: Arm C (Experimental ARM-Annual Booster) Experimental Treatment 2 Interventions

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.

Group II: Arm B (Experimental ARM-No Booster) Experimental Treatment 2 Interventions

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.

Group III: Arm A (Standard ARM- No Booster) Active Control 1 Intervention

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.

Pneumococcal 13-valent Conjugate Vaccine is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺 Approved in European Union as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

🇺🇸 Approved in United States as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

🇨🇦 Approved in Canada as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

🇯🇵 Approved in Japan as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

🇨🇳 Approved in China as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

🇨🇭 Approved in Switzerland as Prevnar 13 for:

• Invasive pneumococcal disease
• Community-acquired pneumonia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Ohio State University Comprehensive Cancer Center Columbus, OH

Who Is Running the Clinical Trial?

Seema Bhat Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pneumococcal conjugate vaccine triggers a better immune response than pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia A randomized study by the Swedish CLL group. [2018] To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent pneumococcal conjugated vaccine (PCV13), Prevenar13®, compared to a 23-valent pneumococcal polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response.

2. Poland pubmed.ncbi.nlm.nih.gov

Assessment of the influence of peripheral blood mononuclear cell stimulation with Streptococcus pneumoniae polysaccharides on expression of selected Toll-like receptors, activation markers and Fas antigen in patients with chronic lymphocytic leukemia. [2019] Since 2012, both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) have been recommended for pneumococcal infection prevention in patients with chronic lymphocytic leukemia (CLL). Available literature data indicate that leukemic cells may respond to the presence of pathogens through specific Toll-like receptors (TLR).

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunogenicity of the 13-Valent Pneumococcal Conjugated Vaccine Followed by the 23-Valent Polysaccharide Vaccine in Chronic Lymphocytic Leukemia. [2023] Patients with Chronic Lymphocytic Leukemia (CLL) have a 29- to 36-fold increased risk of invasive pneumococcal disease (IPD) compared to healthy adults. Therefore, most guidelines recommend vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine (PPSV23). Because both CLL as well as immunosuppressive treatment have been identified as major determinants of immunogenicity, we aimed to assess the vaccination schedule in untreated and treated CLL patients. We quantified pneumococcal IgG concentrations against five serotypes shared across both vaccines, and against four serotypes unique to PPSV23, before and eight weeks after vaccination. In this retrospective cohort study, we included 143 CLL patients, either treated (n = 38) or naive to treatment (n = 105). While antibody concentrations increased significantly after vaccination, the overall serologic response was low (10.5%), defined as a ≥4-fold antibody increase against ≥70% of the measured serotypes, and significantly influenced by treatment status and prior lymphocyte number. The serologic protection rate, defined as an antibody concentration of ≥1.3 µg/mL for ≥70% of serotypes, was 13% in untreated and 3% in treated CLL patients. Future research should focus on vaccine regimens with a higher immunogenic potential, such as multi-dose schedules with higher-valent T cell dependent conjugated vaccines.

4. United States pubmed.ncbi.nlm.nih.gov

Antibody response to the 23-valent pneumococcal polysaccharide vaccine after conjugate vaccine in patients with chronic lymphocytic leukemia. [2023] The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.

5. United States pubmed.ncbi.nlm.nih.gov

Antibody and plasmablast response to 13-valent pneumococcal conjugate vaccine in chronic lymphocytic leukemia patients--preliminary report. [2018] Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60-80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects.

6. United States pubmed.ncbi.nlm.nih.gov

Thirteen-Valent Pneumococcal Conjugate Vaccine in Children With Acute Lymphoblastic Leukemia: Protective Immunity Can Be Achieved on Completion of Treatment. [2021] Children with acute lymphoblastic leukemia (ALL) are at increased risk of developing invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy.