PCV13 + CAR T-Cell Therapy for Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Disqualifiers: Pregnancy, Immunodeficiency, Severe allergy, others
No Placebo Group
Prior Safety Data
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests if a pneumonia vaccine given before and after a special cancer treatment can help patients with difficult-to-treat blood cancers.
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.
What data supports the effectiveness of the treatment PCV13 + CAR T-Cell Therapy for Lymphoma?
Research shows that CD19-targeted CAR T-cell therapies, like axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with aggressive B-cell lymphomas, increasing cure rates from 10% to 40% and demonstrating durable responses in clinical trials.
12345Is CAR T-cell therapy safe for humans?
CAR T-cell therapy, including treatments like tisagenlecleucel and axicabtagene ciloleucel, has been approved for certain types of lymphoma and leukemia, but it can cause significant side effects. Common side effects include cytokine release syndrome (a severe immune reaction) and neurological issues, which require careful management by trained medical teams.
14678How does the PCV13 + CAR T-Cell Therapy for Lymphoma differ from other treatments?
This treatment is unique because it combines a vaccine (PCV13) with CAR T-cell therapy, which uses modified immune cells to target and destroy cancer cells. CAR T-cell therapy is particularly novel for its ability to induce long-lasting remissions in patients with aggressive lymphomas that do not respond to traditional chemotherapy.
13469Eligibility Criteria
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.
+2 more
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
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Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment2 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, United States, United States, 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
References
Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma. [2023]CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a highly effective therapy for patients with relapsed/refractory large B-cell lymphoma (LBCL) and three CD19 CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel) are currently approved for this indication. Despite the clinical benefit of CD19 directed CAR T-cell therapy, this treatment is associated with significant morbidity from treatment-emergent toxicities.
CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences. [2023]Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, and their use has increased the cure rate for these cancers from 10 to 40%. Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020. The commercial availability of the first two products has facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas, shed light on anti-CD19 CAR T-cell products' feasibility in trial-ineligible patients, and raised the need for strategies to mitigate the adverse effects associated with anti-CD19 CAR T-cell therapy, such as cytokine release syndrome, neurotoxicity, and cytopenia. In addition, promising clinical data supporting the use of anti-CD19 CAR T-cell therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukemia have recently become available, breaking the paradigm that these conditions are not curable. Multiple clinical CAR T-cell therapy-based trials are ongoing. These include studies comparing CAR T-cell therapy to autologous stem cell transplantation or investigating their use at earlier stages of disease, novel combinations, and novel constructs. Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.
Value in Using CAR T Cells for DLBCL. [2019]The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma. Three months after the therapy, 32% of the patients showed complete responses and 6% showed partial responses. After 6 months, those rates were 30% and 7%.
CAR T Cell Toxicity: Current Management and Future Directions. [2020]By late 2018, 2 chimeric antigen receptor T (CAR T) cell products have been approved by US and European regulatory authorities. Tisagenlecleucel (Kymriah, Novartis) is indicated in the treatment of patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, or adult patients with large B-cell lymphoma relapsed or refractory (r/r) after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel (Yescarta, Kite) is indicated for the treatment of adult patients with large B-cell lymphoma relapsed or refractory after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (ZUMA-1 trial). This review will offer a practical guide for the recognition and management of the most important toxicities related to the use of the current commercial CAR T cells, and also highlight strategies to diminish these side effects in the future.
[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]Following the first demonstration of efficacy of anti-CD19-directed chimeric antigen receptor (CAR) T cells in a patient with relapsed chronic lymphocytic leukemia (CLL) in 2011, pivotal studies for this innovative therapy were initially conducted in multiple relapsed or refractory (r/r) childhood and young adult acute B‑cell leukemia and in aggressive adult B‑cell lymphoma. The studies demonstrated efficacy even in chemotherapy-refractory disease, resulting in the first approval of autologous and genetically engineered T cells for the treatment of r/r B‑cell acute lymphoblastic leukemia (B-ALL) in the US for the product tisagenlecleucel (Kymriah®, Novartis) back in 2018. Approval for the treatment of r/r aggressive B‑cell lymphoma followed shortly thereafter for tisagenlecleucel and axicabtagene ciloleucel (Yescarta, Kite/Gilead). This review focuses on the treatment of aggressive B‑cell lymphoma and other CD19 positive B‑cell lymphomas by summarizing the study results of clinically tested CAR T cells, discussing possible resistance mechanisms, and providing an outlook on ongoing studies with new target antigens for the treatment of B‑cell lymphomas.
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. [2020]Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.
Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020]Chimeric antigen receptor (CAR)-T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into the patient, the CAR-expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR-T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti-CD19 CAR-T cell therapy that was recently approved in the United States for the treatment of pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Tisagenlecleucel has shown robust in vivo expansion and long-term persistence, clinically meaningful durable response and remission rates, and overall survival benefit in pediatric and young adult patients with relapsed/refractory B-ALL and in relapsed/refractory diffuse large B-cell lymphoma. Common adverse events (AEs) include cytokine release syndrome, which may require hospitalization and admission to an intensive care unit, neurological toxicities, and B-cell aplasia. These AEs are manageable when treated by an appropriately trained team. Additional research is required to further develop AE management protocols. In this review, we describe regulatory requirements, clinical considerations, and site-level requirements for clinical study implementation of CAR-T cell therapy in Europe. We also provide a case study of the European experience from the first global clinical trial for tisagenlecleucel, which may serve as a useful starting point for investigators and clinicians looking to implement CAR-T cell therapy at their institutions.
[Practical aspects of the application of CAR T cells and management of their toxicities]. [2021]CD19 CAR T cells induce - in part long-lasting - remissions in heavily pretreated patients with relapsed/refractory B-cell malignancies. However, they are associated with unique toxicities, and patient management therefore requires specific expertise.In this review, we outline the basics of their mode of action and present the currently available data on their efficacy in various B-cell and plasma cell malignancies. Currently approved therapies (Tisagenlecleucel, Axicabtagene ciloleucel, Brexucabtagene autoleucel) for patients are outlined as well as indications where approvals are expected in the near future. We discuss practical aspects of CAR T cell therapy from the patient's initial presentation, over leukapheresis, to CAR T cell transfusion. Additionally, we highlight the pathophysiology and principles of the management of the most common toxicities (cytokine release syndrome [CRS], immune cell associated neurotoxicity syndrome [ICANS] and cytopenias).
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor which targets the modified T-cell against a specified cancer antigen. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be induced in patients with previously incurable chemotherapy-refractory disease. Three anti-CD19 CAR T-cells are currently Food and Drug Administration and European Medicines Agency approved or in advanced-stage development: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Although all targeting CD19 on the surface of malignant (and healthy) B-cells, these products differ from one another in multiple ways including construct, manufacturing, dose, design of pivotal clinical trials, and toxicity profile. Efficacy and safety data for anti-CD19 CAR T-cell therapy in aggressive B-cell lymphomas will be reviewed, as well as novel CAR T-cell designs and strategies for overcoming treatment resistance.