CAR T-Cell Therapy for Lymphoma and Leukemia
Recruiting in Palo Alto (17 mi)
Overseen byJohn Lister, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: John Lister
Must not be taking: Anticancer, Corticosteroids, Immunosuppressants, others
Disqualifiers: HIV, Hepatitis B, Hepatitis C, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial uses CAR T-cell therapy, which involves modifying a patient's immune cells to fight cancer. It targets patients with B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia who may not respond to standard treatments. The treatment works by collecting, modifying, and reinfusing the patient's own immune cells to attack cancer cells. CAR T-cell therapy has shown remarkable success in treating B-cell malignancies, including B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
Will I have to stop taking my current medications?
The trial requires that you stop certain medications, such as anti-cancer therapies, corticosteroids, and immunosuppressive drugs, at least 4 weeks before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team to see if they need to be paused.
What data supports the effectiveness of the treatment CAR T-Cell Therapy for Lymphoma and Leukemia?
CAR T-cell therapies like Tisagenlecleucel (Kymriah) and Axicabtagene ciloleucel (Yescarta) have been approved for treating certain types of lymphoma and leukemia, showing effectiveness in patients with relapsed or refractory conditions. These treatments have transformed care for aggressive B-cell lymphomas and are specifically authorized for use in cases where other treatments have failed.
12345Is CAR T-Cell Therapy safe for humans?
CAR T-Cell Therapy has been approved for certain types of lymphoma and leukemia, but it can have side effects. Some known side effects include cytopenias (low blood cell counts) and B-cell aplasia (loss of B cells), and there are strategies to manage these. Ongoing monitoring is important to manage potential long-term side effects.
34567How is CAR T-Cell Therapy different from other treatments for lymphoma and leukemia?
CAR T-Cell Therapy is unique because it uses the patient's own immune cells, which are genetically modified to better recognize and attack cancer cells. This personalized approach, known as 'living drugs', is different from traditional treatments like chemotherapy, as it specifically targets cancer cells and can be administered in an outpatient setting.
24578Eligibility Criteria
Adults aged 18-79 with certain types of B-cell lymphoma or acute lymphoblastic leukemia that lack curative treatment options and have a life expectancy under two years. They must not be eligible for commercial CAR T-cell therapy, have measurable disease, and be able to understand the trial. Pregnant women, those unable to consent, or patients with active central nervous system cancer are excluded.Inclusion Criteria
Your CD3 count in your blood is higher than 200/µL.
Subjects must have an expected survival > 12 weeks
I have B-cell cancer with no cure and am expected to live less than 2 years.
+15 more
Exclusion Criteria
You have an active hepatitis B infection.
I have leukemia or lymphoma in my brain that hasn't been treated.
I haven't had cancer treatment within 4 weeks before my leukapheresis.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Cell Collection and Manufacturing
Cell collection by apheresis followed by CAR T-cell manufacturing
4-6 weeks
Lymphodepleting Chemotherapy
Participants receive lymphodepleting chemotherapy prior to CAR T-cell infusion
1 week
Treatment
CAR T-cell infusion on day 0 followed by monitoring for CRS, ICANS, and other toxicity
30 days
Daily visits in hospital from day 0 to day 14, then daily or thrice weekly to day 30
Follow-up
Participants are monitored for safety and effectiveness after treatment
100 days
Monthly clinical examinations to day 100
Long-term Follow-up
Clinical follow-up every 3 months to day 730, then every 6 months to 5 years, and yearly up to 15 years
15 years
Participant Groups
The trial is testing locally manufactured CAR T-cells in treating various forms of B-cell lymphoma and acute lymphoblastic leukemia. It aims to show this method can safely create and administer these cells to help manage these cancers when other treatments aren't available.
1Treatment groups
Experimental Treatment
Group I: Treatment ArmExperimental Treatment1 Intervention
CAR -T-cell collection, infusion
Chimeric Antigen Receptor (CAR) T-Cell Product (Autologous) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as CAR T-Cell Therapy for:
- B-Cell Lymphoma
- B-Acute Lymphoblastic Leukemia
- Multiple Myeloma
- Mantle Cell Lymphoma
🇪🇺 Approved in European Union as CAR T-Cell Therapy for:
- B-Cell Lymphoma
- B-Acute Lymphoblastic Leukemia
- Multiple Myeloma
- Mantle Cell Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
AHN Cancer Institute - West Penn HospitalPittsburgh, PA
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Who Is Running the Clinical Trial?
John ListerLead Sponsor
Allegheny Health NetworkCollaborator
Lentigen Technology, Inc.Collaborator
AHN (Allegheny Health Network) Cancer InstituteCollaborator
Miltenyi Biotec, Inc.Industry Sponsor
References
An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. [2021]Label="PURPOSE OF THE STUDY">Two chimeric antigen receptor (CAR) T-cell therapies - Tisagenlecleucel (Kymriah™) and Axicabtagene ciloleucel (Yescarta™) - have been approved for commercial use. In order to inform forthcoming EBMT guidelines on the management of adults and children undergoing autologous CAR T-cell therapy, we undertook a survey of experienced clinicians.
Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. [2021]CAR T-cells have transformed the therapeutic landscape for patients with relapsed/refractory aggressive B-cell lymphomas. Currently, three CAR T-cell products are approved or soon to be approved: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. These products differ in construct, manufacturing, clinical trial design and toxicity profile. Patient selection for CAR T-cells, and the ideal product for a given patient, involves myriad considerations including age, fitness, prior therapies, comorbid diseases, organ function, logistics of administration, turnaround time, and institutional familiarity. This article reviews the proper patient and product selection for the management of patients with relapsed/refractory aggressive B-cell lymphomas.
[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. [2021]The chimeric antigen receptor T-cells are a new class of anticancer treatment consisting in genetically modifying autologous or allogenic T-cells to make express a CAR directed against a membrane tumor antigen. In Europe, tisagenlecleucel (KymriahTM) has a marketing authorization for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia in children and young adults and of R/R diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (YescartaTM) is the treatment of DLBCL and primary R/R mediastinal B-cell lymphoma. The two products are autologous T-cells directed against CD19. This collaborative work, part of a series of expert opinion-based work, aims to give practical advice to help centers in selection of patients for commercially available CAR T-cell treatment.
[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. [2021]Chimeric antigen receptor (CAR) T-cells are a new class of cancer treatments manufactured through autologous or allogeneic T cells genetic engineering to induce CAR expression directed against a membrane antigen present at the surface of malignant cells. In Europe, tisagenlecleucel (Kymriah™) has a marketing authorization for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and young adults and for the relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta™) is the treatment of relapsed/refractory DLBCL and mediastinal B-cell lymphoma. Both products are "living drugs" and genetically modified autologous T cells directed against CD19 which is an antigen expressed throughout B lymphoid differentiation and on many B malignancies. This collaborative work - part of a series of expert works on the topic - aims to provide practical advice to assist collection facilities that procure the starting material i.e. blood mononuclear cells for autologous CAR T-cell manufacturing.
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.
Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. [2022]Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.
[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. [2022]Chimeric antigen receptor (CAR) T cells are a new class of anti-cancer therapy that involves manipulating autologous or allogeneic T cells to express a CAR directed against a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) has marketing authorization for the treatment of relapsed / refractory acute lymphoblastic leukemia (ALL) in children and young adults, in addition to the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the marketing authorization for axicabtagene ciloleucel (Yescarta™) is for the treatment of relapsed / refractory high-grade B-cell lymphoma and for the treatment of primary mediastinal B-cell lymphoma. Both cell products are genetically modified autologous T cells directed against CD19. These recommendations, drawn up by a working group of the Francophone Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC) relate to the management of patients and the supply chain: medium-term complications, in particular cytopenias and B-cell aplasia, nursing and psychological supportive care. In another work, we will address long-term monitoring, post-marketing authorization pharmacovigilance and issues relating to JACIE and regulatory authorities. These recommendations are not prescriptive; their aim is to provide guidelines for the use of this new therapeutic approach. The purpose of this workshop is to outline the organizational aspects of this new therapeutic approach.
Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]Chimeric antigen receptor T-cell therapy (CAR T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, substantial resources are necessary for administration and care of these patients. Our institution has administered tisagenlecleucel primarily in an outpatient setting, and here we report our clinical outcomes.