Pneumococcal Vaccination for Chronic Lymphocytic Leukemia

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seema Bhat

Must not be taking: H2-blockers, Immunosuppressants

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

80 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 3 5 6}

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. ^{1 2 3 4 5}

Research Team

Seema A. Bhat

Principal Investigator

Ohio State University Comprehensive Cancer Center

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.

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)

Treatment Details

Interventions

• Pneumococcal 13-valent Conjugate Vaccine
• Pneumococcal Polyvalent Vaccine

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

Seema Bhat

Lead Sponsor

Trials

2

Recruited

140+

Findings from Research

In a study of 128 untreated chronic lymphocytic leukemia (CLL) patients, the 13-valent pneumococcal conjugated vaccine (PCV13) produced a significantly stronger immune response compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for most serotypes, both one and six months after vaccination.

Both vaccines were well tolerated, but PCV13 is recommended for inclusion in vaccination programs for CLL patients due to its superior efficacy in eliciting immune responses against Streptococcus pneumoniae.

NCBI (Pubmed)

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. Svensson, T., Kättström, M., Hammarlund, Y., et al.[2018]

In a study of 30 untreated patients with chronic lymphocytic leukemia (CLL), stimulation with the PPV23 vaccine led to significant changes in T and B cell activation markers, indicating a robust immune response.

Specifically, the study found that PPV23 stimulation increased the activation of B cells (CD19+CD69+) and the expression of CD95, suggesting that the vaccine may enhance immune function in CLL patients through Toll-like receptor pathways.

NCBI (Pubmed)

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. Grywalska, E., Hymos, A., Korona-Głowniak, I., et al.[2019]

In a study of 143 patients with Chronic Lymphocytic Leukemia (CLL), vaccination with PCV13 and PPSV23 resulted in a low overall serologic response of only 10.5%, indicating limited effectiveness in generating protective antibodies against pneumococcal disease.

The serologic protection rate was notably low, with only 13% of untreated CLL patients and 3% of treated patients achieving sufficient antibody levels, suggesting a need for improved vaccination strategies, such as multi-dose regimens with more effective vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of the 13-Valent Pneumococcal Conjugated Vaccine Followed by the 23-Valent Polysaccharide Vaccine in Chronic Lymphocytic Leukemia. Haggenburg, S., Garcia Garrido, HM., Kant, IMJ., et al.[2023]

In a study involving 24 patients with chronic lymphocytic leukemia (CLL), the 23-valent pneumococcal polysaccharide vaccine (PPV23) given five years after the 7-valent conjugate vaccine (PCV7) did not significantly improve antibody responses against invasive pneumococcal disease (IPD).

Only 10% to 15% of CLL patients showed an antibody response considered protective after receiving PPV23, indicating that this vaccination strategy is ineffective for enhancing immunity in CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody response to the 23-valent pneumococcal polysaccharide vaccine after conjugate vaccine in patients with chronic lymphocytic leukemia. Lindström, V., Aittoniemi, J., Salmenniemi, U., et al.[2023]

In a study of 24 treatment-naive CLL patients, 58.3% showed an adequate immune response to the PCV13 vaccine, compared to 100% of healthy subjects, indicating a reduced but still significant response in CLL patients.

The PCV13 vaccine was found to be safe, with no significant side effects reported, and it is recommended to be administered early after CLL diagnosis to enhance the likelihood of a better immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody and plasmablast response to 13-valent pneumococcal conjugate vaccine in chronic lymphocytic leukemia patients--preliminary report. Pasiarski, M., Rolinski, J., Grywalska, E., et al.[2018]

Children with acute lymphoblastic leukemia (ALL) show a significantly better immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) when vaccinated at the end of chemotherapy, with 59.5% achieving a protective response one month post-vaccination.

Vaccination during maintenance chemotherapy resulted in a very low protective response (12.8%), indicating that the timing of vaccination is crucial for effective immunization against invasive pneumococcal disease in these children.

NCBI (Pubmed)

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. Bate, J., Borrow, R., Chisholm, J., et al.[2021]

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]

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]

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]

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]

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]

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]