Pneumonia Vaccines for CLL

Recruiting in Palo Alto (17 mi)

Overseen by Daniel Ermann, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Utah

Must be taking: Venetoclax

Must not be taking: Immunosuppressives

Disqualifiers: Severe allergic reaction, Active infection, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether the pneumococcal pneumonia vaccine series (PCV20 and PPSV23) works to mount an effective immune response in patients with chronic lymphocytic leukemia. PCV20 and PPSV23 are both vaccines that protect against bacteria that cause pneumococcal disease. Giving these vaccinations as series may make a stronger immune response and prevent against pneumococcal infections in patients with chronic lymphocytic leukemia.

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.

What data supports the effectiveness of the treatment Pneumococcal 13-valent Conjugate Vaccine and Pneumococcal Polyvalent Vaccine for patients with chronic lymphocytic leukemia (CLL)?

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 CLL. Although the overall immune response is low, PCV13 followed by PPSV23 is recommended to help prevent pneumococcal infections in these patients.

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Is the pneumonia vaccine safe for people with chronic lymphocytic leukemia (CLL)?

The pneumonia vaccines, PCV13 and PPSV23, are generally recommended for people with CLL to prevent infections, and they have been used since 2012. While the immune response may be lower in CLL patients, the vaccines are considered safe for use in humans.

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How does the pneumococcal vaccine treatment for CLL differ from other treatments?

The pneumococcal conjugate vaccine (PCV13) triggers a better immune response in patients with chronic lymphocytic leukemia (CLL) compared to the pneumococcal polysaccharide vaccine (PPSV23), making it more effective in preventing infections in these patients.

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Eligibility Criteria

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 am 18 years old or older.

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

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Huntsman Cancer Institute/University of Utah Salt Lake City, UT

Who Is Running the Clinical Trial?

University of Utah Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. United States 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. [2021] For the current study, the authors sought to determine whether administration of multiple-dose granulocyte-macrophage-colony-stimulating factor (GM-CSF) could improve response to standard 23-valent polysaccharide pneumococcal vaccine (PPV) in patients with chronic lymphocytic leukemia (CLL).

2. 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.

3. 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).

4. 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.

5. 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.

6. 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.

7. New Zealand pubmed.ncbi.nlm.nih.gov

13-Valent Pneumococcal Conjugate Vaccine: A Review of Its Use in Adults. [2018] The 13-valent pneumococcal conjugate vaccine (Prevenar 13(®), Prevnar 13(®)) [PCV13] consists of 13 serotype-specific polysaccharides of Streptococcus pneumoniae (pneumococcus), each covalently conjugated to a non-toxic immunogenic carrier protein. PCV13 has a well established immunogenicity and tolerability profile in adults, particularly those ≥50 years of age. Results of CAPiTA, a randomized, double-blind, placebo-controlled trial in >84,000 older adults aged ≥65 years, showed that PCV13 was effective in preventing vaccine-type pneumococcal community-acquired pneumonia (CAP), vaccine-type pneumococcal nonbacteraemic (noninvasive) CAP and vaccine-type invasive pneumococcal disease (IPD). These findings, along with changes in pneumococcal serotype distribution and epidemiology of pneumococcal disease, prompted the US Advisory Committee on Immunization Practices (ACIP) to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPVS23) for all adults aged ≥65 years. PCV13 also has a role in preventing pneumococcal disease (pneumonia and IPD) in younger adults with immunocompromising conditions and potentially in those with other underlying medical conditions that increase the risk of pneumococcal disease.