Pneumonia Vaccines for CLL

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: Venetoclax

Must not be taking: Immunosuppressives

Disqualifiers: Severe allergic reaction, Active infection, 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: 8

Duration: 9 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two pneumonia vaccines, PCV20 and PPSV23 (Pneumococcal Polyvalent Vaccine), can enhance the immune system to better protect against infections in people with chronic lymphocytic leukemia (CLL). The study tests the effectiveness of these vaccines in two groups: those who have never been treated for CLL and those currently or previously treated with venetoclax. Individuals with CLL who have not yet received treatment or have been on venetoclax for at least a year might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use immunosuppressive medication within 14 days before starting the trial, except for certain allowed steroids.

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

Research has shown that the pneumococcal vaccines in this study, PCV20 and PPSV23, are generally well-tolerated. PCV20, or the 20-valent pneumococcal conjugate vaccine, was tested in adults over 65 years old. Most participants did not experience serious side effects, with only about 2.5% reporting any serious issues, which is quite low. Individuals should not receive PCV20 if they have had a severe allergic reaction to it or any of its ingredients.

PPSV23, also known as the pneumococcal polyvalent vaccine, is approved for people 50 years or older and for children two years and above who are at risk. This vaccine has been used for a long time, and most reported side effects are mild. Both vaccines aim to protect against pneumococcal disease, a serious infection caused by bacteria.

Overall, these vaccines have a good safety record, and serious problems are rare. However, because everyone is different, it is important to discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore new ways to protect CLL patients from pneumonia, a serious risk for them. Unlike standard vaccines, the investigational treatments include a pneumococcal 20-valent conjugate vaccine, which covers more strains of the bacteria that cause pneumonia, potentially offering broader protection. Additionally, the combination of this vaccine with the pneumococcal polyvalent vaccine aims to enhance immune response, especially in patients undergoing venetoclax therapy. By targeting more bacterial strains and boosting immune efficacy, these treatments could significantly reduce pneumonia-related complications in CLL patients.

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

Research shows that people with chronic lymphocytic leukemia (CLL) face a much higher risk of serious infections from pneumococcal bacteria. In this trial, participants will receive either the pneumococcal 20-valent conjugate vaccine (PCV20) followed by the pneumococcal polyvalent vaccine (PPSV23) or the same sequence with different timing. Previous studies have found that the pneumococcal conjugate vaccine (PCV13) generates a strong immune response in CLL patients, often outperforming the pneumococcal polysaccharide vaccine (PPSV23). In CLL patients, antibody levels remain higher even a year after revaccination, suggesting long-lasting protection. Studies also indicate that survival rates improve significantly in CLL patients who receive these vaccines. Overall, these vaccines show promise in protecting against pneumococcal infections in people with CLL. ^{6 7 8 9 10}

Who Is on the Research Team?

Daniel Ermann, MD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for adults aged 18+ with chronic lymphocytic leukemia who haven't had prior CLL treatment, or those treated with venetoclax for at least a year. Participants should not have used immunosuppressants recently, except certain steroids, and mustn't have had specific pneumonia vaccines in the last five years.

Inclusion Criteria

I have been treated with venetoclax for at least a year and my last dose was within the last 12 months.

I have been diagnosed with CLL or SLL as per the 2018 guidelines.

I have never received treatment for chronic lymphocytic leukemia.

Exclusion Criteria

I am currently on antibiotics for an infection.

I have had a pneumococcal vaccine (PCV13 or PCV20) in the last 5 years, or PPSV23 over a year ago.

I haven't taken strong immune-suppressing drugs recently, except for some allowed minor uses or low-dose steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive pneumococcal 20-valent conjugate vaccine on day 1 and pneumococcal polyvalent vaccine on day 60

9 weeks

2 visits (in-person)

Follow-up

Participants are monitored for immune response and safety after vaccination

5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pneumococcal 13-valent Conjugate Vaccine
• Pneumococcal Polyvalent Vaccine

Trial Overview The PROTECT CLL Trial is testing if a series of two pneumococcal vaccines (PCV20 and PPSV23) can effectively stimulate an immune response to prevent infections in patients with chronic lymphocytic leukemia.

How Is the Trial Designed?

Group I: Arm II (PCV20, PPPSV23) Experimental Treatment 3 Interventions

Patients who have received or are receiving venetoclax therapy, receive pneumococcal 20-valent conjugate vaccine IM at study visit 1 and pneumococcal polyvalent vaccine IM at study visit 2 in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (PCV20, PPSV23) Experimental Treatment 3 Interventions

Patients receive pneumococcal 20-valent conjugate vaccine IM on day 1. PnumoVax23 will be given as an intramuscular injection on Visit 2 (approximately Day 75)

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?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

The 13-valent pneumococcal conjugate vaccine (PCV13) has been shown to be effective in preventing various forms of pneumococcal disease in a large study of over 84,000 adults aged 65 and older, demonstrating its strong immunogenicity and safety profile.

Based on its effectiveness and changes in disease patterns, health authorities now recommend PCV13 for all adults aged 65 and older, as well as for younger adults with certain health conditions that increase their risk for pneumococcal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13-Valent Pneumococcal Conjugate Vaccine: A Review of Its Use in Adults. Plosker, GL.[2018]

In a study involving 32 patients with chronic lymphocytic leukemia (CLL), the addition of multiple doses of GM-CSF to the standard pneumococcal vaccine did not significantly improve the immune response, as less than 10% of patients showed a 4-fold increase in antibody levels.

Despite the low response to the vaccine, the administration of GM-CSF was associated with only minor side effects, indicating that it is a safe intervention in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple-dose granulocyte-macrophage-colony-stimulating factor plus 23-valent polysaccharide pneumococcal vaccine in patients with chronic lymphocytic leukemia: a prospective, randomized trial of safety and immunogenicity. Safdar, A., Rodriguez, GH., Rueda, AM., et al.[2021]

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]

Citations

1. 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 ...

2. 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.

3. 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, ...

4. 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.

5. 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).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05183854

Pneumococcal Pneumonia Vaccine Series (PCV20 and ... Giving these vaccinations as series may make a stronger immune response and prevent against pneumococcal infections in patients with chronic lymphocytic ...

7. cdc.gov cdc.gov/mmwr/volumes/71/wr/mm7104a1.htm

Use of 15-Valent Pneumococcal Conjugate Vaccine and ... The rates of serious adverse events (SAEs) within 6 months of vaccination were 2.5% among PCV15 recipients and 2.4% among PCV13 recipients. No ...

8. haematologica.org haematologica.org/article/view/11968

Revaccination with pneumococcal conjugate vaccine five ... Our findings suggest that repeated doses of a T-cell-dependent pneumococcal vaccine improve protection in CLL patients. The study is registered ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507794/

Pneumococcal Vaccine - StatPearls - NCBI Bookshelf A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different ...

10. prevnar20.com prevnar20.com/

PREVNAR 20® (Pneumococcal 20-Valent Conjugate Vaccine ... IMPORTANT SAFETY INFORMATION · Prevnar 20 should not be given to anyone who has had a severe allergic reaction to any component of Prevnar 20 or to diphtheria ...