CAR T Cell Therapy for Large B-Cell Lymphoma
(ALPHA2 Trial)
Recruiting in Palo Alto (17 mi)
+26 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Allogene Therapeutics
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had systemic anti-cancer therapy within 2 weeks before receiving ALLO-647.
What data supports the idea that CAR T Cell Therapy for Large B-Cell Lymphoma is an effective treatment?
The available research shows that CAR T Cell Therapy is an effective treatment for Large B-Cell Lymphoma. In a study comparing CAR T Cell Therapy to another treatment called alloHCT, patients who received CAR T Cell Therapy had a longer median survival time of 475 days compared to 285 days for those who received alloHCT. Additionally, after receiving the treatment, 68% of CAR T Cell patients were still alive after 12 months, compared to 54% of alloHCT patients. This suggests that CAR T Cell Therapy may be a better option for patients with this type of lymphoma.
12345What safety data is available for CAR T Cell Therapy in treating large B-cell lymphoma?
CAR T Cell Therapy, specifically targeting CD19, has been evaluated for safety in various studies. The therapy is associated with some adverse events, including cytokine release syndrome (33-69%), neurotoxicity (8-33%), and B-cell aplasia (54%). However, the therapy has shown a good safety profile in some trials, with no serious adverse events directly attributed to the treatment and no dose-limiting toxicities reported. The risk of graft-versus-host disease is low, especially with off-the-shelf CAR T-cell therapies. Infectious complications are a concern, and optimal antimicrobial prophylaxis strategies are still being studied.
678910Is the treatment ALLO-501A a promising treatment for large B-cell lymphoma?
Yes, ALLO-501A, a type of CAR T-cell therapy, is a promising treatment for large B-cell lymphoma. It uses specially modified immune cells to target and fight cancer cells, offering new hope for patients who have not responded to other treatments.
311121314Eligibility Criteria
Adults with relapsed or refractory large B-cell lymphoma who have tried at least two chemotherapy treatments can join. They should be relatively healthy (ECOG status 0 or 1), not have had certain recent treatments like radiation, and must not have active infections or other cancers treated in the last three years.Inclusion Criteria
I am fully active or can carry out light work.
My condition did not improve after 2 different chemotherapy treatments.
My blood, kidney, and liver tests are within normal ranges.
+3 more
Exclusion Criteria
I haven't had any cancer treatments in the last 2 weeks.
I have a thyroid disorder, but it's controlled with stable hormone therapy.
I had a stem cell transplant using my own cells within the last 6 months.
+6 more
Participant Groups
The ALPHA-2 study is testing ALLO-501A CAR T cells after a prep treatment with fludarabine, cyclophosphamide, and ALLO-647. The goal is to see if this new therapy is safe and effective for patients whose lymphoma has come back or hasn't responded to previous treatments.
1Treatment groups
Experimental Treatment
Group I: ALLO-501A, ALLO-647Experimental Treatment4 Interventions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Harvard Massachusetts General HospitalBoston, MA
Montefiore Einstein Center for Cancer CareBronx, NY
Advent HealthOrlando, FL
UCLA Medical CenterLos Angeles, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Allogene TherapeuticsLead Sponsor
References
CAR T cells or allogeneic transplantation as standard of care for advanced large B-cell lymphoma: an intent-to-treat comparison. [2021]CD19-directed chimeric antigen receptor (CAR) T-cell treatment has evolved as standard of care (SOC) for multiply relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, its potential benefit over allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. We compared outcomes with both types of cellular immunotherapy (CI) by intention to treat (ITT). Eligble were all patients with R/R LBCL and institutional tumor board decision recommending SOC CAR T-cell treatment between July 2018 and February 2020, or alloHCT between January 2004 and February 2020. Primary end point was overall survival (OS) from indication. Altogether, 41 and 60 patients for whom CAR T cells and alloHCT were intended, respectively, were included. In both cohorts, virtually all patients had active disease at indication. CI was recommended as part of second-line therapy for 21 alloHCT patients but no CAR T-cell patients. Median OS from indication was 475 days with CAR T cells vs 285 days with alloHCT (P = .88) and 222 days for 39 patients for whom alloHCT beyond second line was recommended (P = .08). Of CAR T-cell and alloHCT patients, 73% and 65%, respectively, proceeded to CI. After CI, 12-month estimates for nonrelapse mortality, relapse incidence, progression-free survival, and OS for CAR T cells vs alloHCT were 3% vs 21% (P = .04), 59% vs 44% (P = .12), 39% vs 33% (P = .97), and 68% vs 54% (P = .32), respectively. In conclusion, CAR T-cell outcomes were not inferior to alloHCT outcomes, whether measured by ITT or from CI administration, supporting strategies preferring CAR T cells over alloHCT as first CI for multiply R/R LBCL.
Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. [2021]The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive.
Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. [2022]CD19-directed chimeric antigen receptor T cells (CAR T) are approved for treatment of adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) following at least two lines of therapy.
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. [2022]CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined.
Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma. [2020]This article will review the use of anti-CD19 CAR-T therapy used in relapsed/refractory diffuse large B cell lymphoma.
Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R/R ALL and NHL: A systematic review and meta-analysis. [2022]Allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has the potential for extensive clinical applications. This study aimed to evaluate its efficacy and safety in treating relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Four databases were searched for relevant studies. Among patients treated with donor-derived CAR T-cell therapy, ALL patients had a complete remission (CR) rate of 80 % and a 1-year overall survival rate of 51 %. The graft-versus-host disease (GvHD) rate was 4 %, cytokine release syndrome was 69 %, and immune effector cell-associated neurotoxicity syndrome was 8 %. For off-the-shelf CAR T-cell therapy, the CR rate for ALL was 70 %, and for NHL, it was 52 %. The objective response rate for NHL was 72 %. The pooled GvHD of off-the-shelf CAR T-cell therapy for ALL and NHL combined was 0 %. Allogeneic anti-CD19 CAR T-cell therapy are effective and safe for treating R/R ALL and NHL. AVAILABILITY OF DATA AND MATERIALS: All datasets generated in this study are included in the article/Supplementary Material.
Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. [2022]Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells.
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.
Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can cause direct and indirect toxic adverse effects and increased risk for infection. Infectious complications and optimal antimicrobial prophylaxis strategies are an ongoing area of investigation.
The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy. [2022]Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T-cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed.
CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]Cellular immunotherapy with CD19-directed chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for aggressive B-cell non-Hodgkin lymphoma (B-NHL). Three CAR T-cell therapies are commercially avai.
Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. [2020]Chimeric antigen receptor (CAR)-T-cell therapy is an innovative form of adoptive cell therapy that has revolutionized the treatment of certain hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). The treatment is currently also being studied in other B-cell neoplasms, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). CD19 and B-cell maturation antigen (BCMA) have been the most popular target antigens for CAR-T-cell immunotherapy of these malignancies. This review will discuss the efficacy and toxicity data from the pivotal clinical studies of CD19- and BCMA-targeted CAR-T-cell therapies in relapsed/refractory B-cell malignancies (NHL, ALL, CLL) and MM, respectively.
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.