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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal vaccination schedule to protect against pneumococcal infections in individuals with chronic lymphocytic leukemia (CLL). It tests whether more frequent vaccinations enhance protection compared to the standard five-year schedule. Participants will receive various combinations and timings of pneumococcal vaccines, including the Pneumococcal 13-valent Conjugate Vaccine (Prevnar 13, PCV13) and the Pneumococcal Polyvalent Vaccine (Pneumovax 23, PPSV23), to identify which provides the best immune response. Suitable candidates for this trial include those with CLL who have not undergone chemotherapy or radiotherapy for it and have an expected life span of more than two years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the pneumococcal vaccines used in the trial are generally safe. Studies have found that the Pneumococcal 13-valent Conjugate Vaccine (PCV13) is safe and helps build a strong defense, even in individuals with blood cancers like leukemia. This includes patients with chronic lymphocytic leukemia (CLL), who often have weaker immune systems.

The Pneumococcal Polyvalent Vaccine (PPSV23), also known as PNEUMOVAX 23, has FDA approval for people aged 50 and older, and for those as young as two who are at higher risk for pneumococcal disease, such as those with leukemia. Safety data show that most people handle these vaccines well, with few serious side effects reported.

While both vaccines are generally well-tolerated, people with CLL might respond differently. The trial aims to determine if changing the vaccination schedule can offer better protection for these patients. However, based on current evidence, both vaccines are considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for chronic lymphocytic leukemia (CLL) because they explore different vaccination strategies to boost the immune response against pneumococcal infections, a common complication in CLL patients. Unlike standard pneumococcal vaccines, which are typically given as single doses, this study explores the potential benefits of combining a 13-valent conjugate vaccine and a polyvalent vaccine, with one group also receiving an annual booster. The treatments aim to enhance long-term immunity by checking antibody levels over five years, offering insights into more effective protection strategies for CLL patients who are often immunocompromised.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that the Pneumococcal 13-valent Conjugate Vaccine (PCV13) generates a strong immune response in people with chronic lymphocytic leukemia (CLL). One study found that PCV13 outperformed another vaccine, PPSV23, in protecting against 10 out of 12 types of pneumococcal bacteria one month after vaccination. Additionally, antibody levels remained higher than pre-vaccination levels for at least a year. In this trial, participants in Arm A will receive PCV 20 without a booster. Arm B participants will receive both PCV 20 and PPSV23 without a booster, while Arm C participants will receive PCV 20, PPSV23, and an annual PPSV23 booster. This combination of vaccines aims to protect CLL patients, who face a much higher risk of serious infections, by enhancing the immune response. Overall, these vaccines are used together in this trial to provide CLL patients with better protection against pneumococcal infections. ^{1 2 6 7 8}

Who Is on the Research Team?

Seema A. Bhat

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

Estimated life expectancy of greater than 24 months

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

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]

Citations

1. ascopost.com ascopost.com/news/march-2021/responses-to-conjugate-pneumococcal-vaccine-in-patients-with-chronic-lymphocytic-leukemia/

Responses to Conjugate Pneumococcal Vaccine in ... Estimated overall survival at 36 months was 86.7%. Poorer survival was associated with prior vs no prior pneumonia (68.5% vs 97.6%, P < .0001).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10385862/

Immunogenicity of the 13-Valent Pneumococcal ... Patients with Chronic Lymphocytic Leukemia (CLL) have a 29- to 36-fold increased risk of invasive pneumococcal disease (IPD) compared to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6037466/

Antibody persistence after pneumococcal conjugate ... This data suggests that PCV could result in antibody persistence at least five years in CLL patients.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X18306194

Pneumococcal conjugate vaccine triggers a better immune ... PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, ...

5. hematologyadvisor.com hematologyadvisor.com/news/chronic-leukemia-cll-tcell-dependent-vaccine-treatment-risk/

Repeated T-Cell Dependent Vaccination Enhances ... Twelve months after revaccination, antibody levels declined but remained significantly higher than baseline in patients with CLL.

6. haematologica.org haematologica.org/article/view/11968

Revaccination with pneumococcal conjugate vaccine five ... Patients with chronic lymphocytic leukemia (CLL) have an impaired response to vaccination, which calls for improved vaccination strategies.

7. cdc.gov cdc.gov/mmwr/volumes/68/wr/mm6846a5.htm

Use of 13-Valent Pneumococcal Conjugate Vaccine and ... ACIP recognized that some adults aged ≥65 years are potentially at increased risk for exposure to PCV13 serotypes, such as persons residing in ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X22001025

Vaccine PCV13 is thus safe and immunogenic, including against serotype 3, in patients with hematological malignancies and solid tumors outside the recommended age ...