CAR-T Therapy for B-Cell Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University Health Network, Toronto
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Autoimmune, Immunodeficiency, Transplant, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests TBI-2001, a therapy that modifies a patient's immune cells to better attack cancer. It targets patients whose cancers have not responded to other treatments. The treatment works by enhancing the immune cells' ability to kill cancer cells.
Will I have to stop taking my current medications?
The trial protocol suggests that you may need to stop certain medications before apheresis and lymphodepleting chemotherapy, following specific guidelines. However, if you are on targeted or biological therapies that don't affect the collection of lymphocytes, you might not need a washout period, but this requires approval from the Sponsor.
What data supports the effectiveness of the treatment CAR-T Therapy for B-Cell Lymphoma?
Research shows that CAR T-cells targeting CD19 have been effective in treating B-cell lymphomas, with some patients experiencing significant tumor regression and prolonged elimination of B-lineage cells. This suggests that CAR-T therapy is a promising approach for treating B-cell malignancies.
12345Is CAR-T therapy for B-cell lymphoma safe?
CAR-T therapy for B-cell lymphoma can cause serious side effects, including neurologic issues and cytokine release syndrome (a severe immune reaction). However, some studies have shown it to be generally safe, with manageable side effects, in certain patient groups.
16789How is the treatment TBI-2001 unique for B-cell lymphoma?
TBI-2001 is a type of CAR T-cell therapy, which uses a patient's own T-cells (a type of immune cell) that are modified to better recognize and attack B-cell lymphoma cells by targeting the CD19 protein on their surface. This approach is different from traditional treatments because it involves engineering the patient's immune cells to fight the cancer, offering a new option for those with relapsed or refractory B-cell lymphoma.
1371011Eligibility Criteria
This trial is for adults over 18 with CD19+ B-cell Lymphoma, CLL, or SLL who've had at least two prior treatments. They should be in good health with a life expectancy of more than 4 months and have not received cancer treatment within the last two weeks. Pregnant women, those with certain medical conditions or history of organ transplant requiring immunosuppression are excluded.Inclusion Criteria
I have B cell cancer and have had at least 2 treatments before.
Phase Ib cohort will enroll CLL/SLL patients only
Life expectancy greater than 4 months
+6 more
Exclusion Criteria
Pregnant or lactating women
Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation
I haven't had any cancer except skin cancer in the last 2 years.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-treatment
Participants receive conditioning chemotherapy with cyclophosphamide and fludarabine
1-2 weeks
Treatment
Participants receive TBI-2001 CAR-T cells intravenously following dose-escalation cohorts
1 week
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Long-term follow-up
Long-term follow-up is conducted for 5 years following the infusion of TBI-2001
5 years
Participant Groups
The study tests TBI-2001 (a CAR-T therapy targeting CD19) along with Cyclophosphamide and Fludarabine in patients whose disease returned after treatment or didn't respond to previous therapies. It's an early-phase trial to check safety and effectiveness, gradually increasing doses to find the right amount.
1Treatment groups
Experimental Treatment
Group I: Experimental: Dose Level 1 to 3Experimental Treatment3 Interventions
0.3 to 3 x 10\^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Princess Margaret Cancer CentreToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
Takara Bio Inc.Industry Sponsor
References
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. [2023]Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited.
CARs and cancers: questions and answers. [2021]In this issue of Blood, Till et al present 3 patients with relapsed B-cell lymphomas treated with autologous T cells genetically modified to express a CD20-targeted chimeric antigen receptor (CAR) demonstrating both safety and clinical efficacy.
T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor (CAR). The CAR contains an antigen recognition part (originating from an antibody), a T-cell receptor transmembrane and cytoplasmic signalling part, and one or more co-stimulatory domains. While CAR T-cells can be directed against any tumour target, most experience thus far has been obtained with targeting of the B-cell antigen CD19 that is expressed by B-cell acute lymphocytic leukaemia, chronic lymphocytic leukaemia and other B-cell lymphomas. The first clinical results are promising, although there are profound differences in response between patients with different haematological malignancies. Treatment-related side effects have been observed that require specific management. This review will explain the mechanism of action, summarise the experience to date and point out future directions for this hopeful new addition to the therapeutic armamentarium in the treatment of lymphoproliferative B-cell malignancies.
Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. [2023]Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.
Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. [2021]Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources.
Economic Burden of Neurologic Toxicities Associated with Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States. [2022]Chimeric antigen receptor (CAR) T-cell therapy, which is approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), can be associated with potentially severe and costly neurologic adverse events (AEs).
Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. [2023]Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a promising treatment in relapsing B-cell lymphoma but is frequently associated with acute neurotoxicity. Neurologic long-term safety has not been thoroughly assessed.
CD19 CAR-T Cell Therapy Induced Immunotherapy Associated Interstitial Pneumonitis: A Case Report. [2022]Chimeric antigen receptor-modified T cells (CAR-T) targeting CD19 has produced a high durable response in refractory or relapsed diffuse large B-cell lymphoma. Besides well-known cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome during CAR-T cell therapy, there were several rarely encountered fatal complications.
Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. [2022]Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.
Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy.
CD19-directed CAR T-cell therapy in B-cell NHL. [2021]CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a valuable new treatment option for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. The aim of this review is to give an overview of the pivotal phase I/II trials, emerging real-world evidence and ongoing trials.