PCV13 + CAR T-Cell Therapy for Lymphoma

Overseen By Lindsey Raymond

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Maintenance chemotherapies, IVIG

Disqualifiers: Pregnancy, Immunodeficiency, Severe allergy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering a pneumonia vaccine (PCV13) before and after CD19-targeted CAR T cell therapy can enhance the immune system's response to certain infections. The focus is on individuals with specific types of lymphoma, a cancer affecting the immune system, who are scheduled to receive this treatment. Those with lymphoma that has not responded to other treatments or has recurred may be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on intravenous immunoglobulin (IVIG), you must not have received it within one month of the planned apheresis for CAR T cell therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are receiving intravenous immunoglobulin (IVIG) or have had the PCV13 vaccine recently, you may need to wait before participating.

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

Research has shown that CD19-targeted CAR T-cell therapy offers promising safety results. Studies have found that patients with aggressive B-cell lymphomas generally tolerate this treatment well. Some side effects, such as fever and low blood pressure, can occur but are usually manageable with medical care.

Similarly, the pneumococcal conjugate vaccine (PCV13) is widely used and has a strong safety record. The FDA has approved it to prevent certain types of pneumonia. Most people experience only minor side effects, such as soreness at the injection site.

Together, these treatments offer a hopeful approach. Both CAR T-cell therapy and the PCV13 vaccine have demonstrated safety in previous studies. Prospective trial participants can feel reassured by this existing evidence. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lymphoma, which often involve chemotherapy and radiation, the combination of PCV13 vaccine and CD19-targeted CAR T-cell therapy offers a novel approach. This treatment works by engineering the patient's own T cells to specifically target and destroy cancer cells marked by the CD19 protein. Researchers are particularly excited because this method has the potential to enhance the body's immune response against lymphoma and reduce the reliance on more toxic treatment options. Additionally, the inclusion of the pneumococcal vaccine aims to boost the immune system, potentially improving the overall effectiveness and safety of the therapy.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that CD19-targeted CAR T-cell therapy, which participants in this trial may receive, greatly improves outcomes for patients with aggressive B-cell lymphomas. Studies have found that this treatment can lead to long-lasting positive effects compared to many other treatments. For instance, one study reported that 39% of patients with a specific type of lymphoma remained alive after five years. This therapy works by modifying a patient's own immune cells to enhance their ability to find and attack cancer cells. Although still under study, these findings suggest that CD19-targeted CAR T-cell therapy is a promising option for treating certain lymphomas. ^{1 2 4 6 7}

Who Is on the Research Team?

Frederick Locke, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of B-cell lymphoma who are in good health or have relapsed/refractory disease and are candidates for CD19-targeted CAR T cell therapy. They must be willing to use effective contraception if applicable, and cannot participate if they have severe allergies to vaccines, active infections, very low blood counts, recent IVIG treatment, or are pregnant.

Inclusion Criteria

I am willing and able to follow all study rules and be available for its duration.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation

I am over 18 years old.

Exclusion Criteria

I do not have any active or uncontrolled infections.

History of severe allergy (e.g., anaphylaxis) to any component of pneumococcal conjugate vaccine 7 valent (PCV7), PCV13, or any diphtheria-toxoid containing vaccine.

Patients with significant psychiatric illness likely to affect compliance, as determined by the treating physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination Pre-Therapy

Participants receive the PCV13 vaccine 7 days (range 4 to 21 days) before apheresis collection

1-3 weeks

1 visit (in-person)

CAR T Cell Therapy

Participants undergo CD19-targeted CAR T cell therapy

1 day

1 visit (in-person)

Vaccination Post-Therapy

Participants receive the PCV13 vaccine on day +30 (range +21 to +37) and day +90 (range +75 to +115) after CAR T cell infusion

3 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CD19 targeted CAR T Cell Therapy
• Pneumococcal conjugate vaccine (PCV13)

Trial Overview The study tests whether the pneumococcal conjugate vaccine (PCV13) given before and after CD19-targeted CAR T cell therapy can improve immune response against pneumococcus in patients with specific types of B-cell lymphoma.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Pneumococcal conjugate vaccine (PCV13) .5 ml will be administered intramuscularly three times: 7 days (range 4 to 21 days) before apheresis collection and on day +30 (range +21 to +37) and day +90 (range +75 to +115) after CAR T cell infusion.

CD19 targeted CAR T Cell Therapy is already approved in United States, European Union, China for the following indications:

Approved in United States as tisagenlecleucel (Kymriah) for:

• B-cell precursor acute lymphoblastic leukemia (B-ALL)
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as axicabtagene ciloleucel (Yescarta) for:

• Large B-cell lymphoma (LBCL)
• Follicular lymphoma (FL)

Approved in United States as lisocabtagene maraleucel (Breyanzi) for:

• Large B-cell lymphoma (LBCL)
• Follicular lymphoma (FL)

Approved in United States as brexucabtagene autoleucel (Tecartus) for:

• Mantle cell lymphoma (MCL)

Approved in European Union as CD19-targeted CAR T-cell therapy for:

• B-cell precursor acute lymphoblastic leukemia (B-ALL)
• Diffuse large B-cell lymphoma (DLBCL)
• Follicular lymphoma (FL)

Approved in China as CD19-targeted CAR T-cell therapy for:

• B-cell acute lymphoblastic leukemia (B-ALL)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

Tisagenlecleucel, an anti-CD19 CAR-T cell therapy, has been approved for treating pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), showing significant long-term effectiveness and overall survival benefits.

While CAR-T cell therapy can lead to serious adverse events like cytokine release syndrome and neurological toxicities, these effects are manageable with proper medical training and protocols, highlighting the importance of specialized care in administering this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. Buechner, J., Kersten, MJ., Fuchs, M., et al.[2020]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

CD19-directed CAR T-cell therapy, particularly axicabtagene ciloleucel, is highly effective for treating relapsed/refractory large B-cell lymphoma, but it comes with significant risks of treatment-emergent toxicities such as cytokine release syndrome and neurotoxicity.

Understanding the safety profile and potential complications of CAR T-cell therapy is crucial for selecting appropriate patients and implementing preventative measures, which can enhance the overall safety and effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma. Nath, K., Wudhikarn, K., Alarcon Tomas, A., et al.[2023]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

CAR T-cell therapy targeting CD19 has significantly improved cure rates for relapsed or refractory aggressive B-cell lymphomas, increasing from 10% to 40% with the use of approved products like axicabtagene ciloleucel and tisagenlecleucel.

There is emerging evidence supporting the use of anti-CD19 CAR T-cell therapy in previously considered incurable conditions like indolent B-cell lymphomas and chronic lymphocytic leukemia, with ongoing trials exploring new treatment strategies and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences. Vitale, C., Strati, P.[2023]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

In the phase II JULIET trial, the CAR T-cell therapy tisagenlecleucel targeting CD19 demonstrated durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma, with 32% achieving complete responses at 3 months.

The efficacy remained stable at 6 months, with 30% of patients still showing complete responses, indicating the potential long-term effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

CD19 CAR T cells can lead to long-lasting remissions in patients with relapsed or refractory B-cell malignancies, but they come with unique toxicities that require specialized management.

Currently approved CAR T cell therapies, such as Tisagenlecleucel and Axicabtagene ciloleucel, are effective but necessitate careful monitoring for side effects like cytokine release syndrome and neurotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Practical aspects of the application of CAR T cells and management of their toxicities]. Bücklein, V., Blumenberg, V., Subklewe, M.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725015283

Who Is Eligible for CAR T-Cell Therapy? Expert ... In patients with R/R mantle cell lymphoma, brexucabtagene autoleucel showed a 60-month OS rate of 39% at 2 × 106 anti-CD19 CAR T cells/kg ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9290945/

Efficacy and safety of CD19‐directed CAR‐T cell therapies in ... Chimeric antigen receptor (CAR)‐T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B‐cell lymphomas.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6502/527482/Outcomes-of-Outpatient-CD19-Targeted-Chimeric

Outcomes of Outpatient CD19-Targeted Chimeric Antigen ... In this study, we aimed to investigate the outcomes after outpatient CD19-targeted CAR T-cell therapy in patients with B-cell lymphomas.

4. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

5. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... However, despite the excellent clinical outcomes observed with several chimeric antigen receptor T (CAR-T) cell products targeting CD19 or BCMA ...

6. lymphomahub.com lymphomahub.com/medical-information/long-term-outcomes-following-car-t-cell-therapy-in-b-cell-malignancies

Long-term outcomes following CAR T-cell therapy in B- ... Data from 12 studies at a median follow-up of 1-year (range, 1–4.8 years) outline the long-term efficacy of CD19-targeted CAR T-cell therapies in B-ALL.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9284423/

CAR T-cell therapy for B-cell lymphoma - PMC - PubMed Central Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene ...