Cell Therapy for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+20 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Miltenyi Biomedicine GmbH
Must not be taking: Systemic corticosteroids
Disqualifiers: HIV, Active hepatitis B, Seizures, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests a new treatment where a patient's own immune cells are enhanced to fight difficult-to-treat lymphoma. It targets patients whose cancer hasn't responded to at least two other treatments. The modified cells aim to better recognize and attack the cancer. This new method improves the ability of the patient's immune cells to find and destroy cancer cells.
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, it mentions that at least 2 weeks or 5 half-lives must have passed since your last systemic therapy before a certain procedure, so it's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment MB-CART2019.1 for Non-Hodgkin's Lymphoma?
Research shows that CAR T-cell therapy targeting CD19 has been very effective for treating aggressive B-cell lymphomas, including Non-Hodgkin's Lymphoma, especially in patients who did not respond to other treatments. This type of therapy has been approved by health authorities and has shown long-lasting remissions in many patients.
12345Is CAR T-cell therapy generally safe for humans?
CAR T-cell therapy, including treatments like axicabtagene ciloleucel and tisagenlecleucel, has shown potential safety concerns such as cytokine release syndrome (a severe immune reaction), neurotoxicity (nerve damage), and infections. While these side effects can be serious, they are not always fatal, and ongoing research aims to better understand and manage these risks.
26789What makes the treatment MB-CART2019.1 unique for non-Hodgkin's lymphoma?
MB-CART2019.1 is unique because it targets both CD19 and CD20 antigens on B-cells, unlike other CAR T-cell therapies that typically target only CD19. This dual targeting approach may enhance the effectiveness of the treatment by addressing potential resistance mechanisms in non-Hodgkin's lymphoma.
123510Eligibility Criteria
Adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least two other treatments without success can join this study. They should not be candidates for a stem cell transplant or must have chosen not to undergo one. Participants need to be over 18, in fairly good health otherwise, and able to follow birth control guidelines during the trial.Inclusion Criteria
Platelet count > 50,000/μL
My condition did not improve after 2 chemotherapy treatments including rituximab and anthracycline, and I either can't have or chose not to have a stem cell transplant.
My total bilirubin level is below 1.5 mg/dl, unless I have Gilbert's syndrome.
+16 more
Exclusion Criteria
I have an autoimmune disease affecting my nervous system.
Previous or concurrent malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry), In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study, Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years, A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years, History of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus)requiring systemic immunosuppressive or system disease modifying agents within the last 2 years, Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day, History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment, Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis, Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline, History of severe immediate hypersensitivity reaction to any of the agents used in this study, Refusal to participate in additional lentiviral gene therapy LTFU protocol, Prior CAR-T therapy for any indication or systemic gene modifying therapy for DLBCL, Prior allogeneic stem cell transplant for any indication, Prior BITE antibodies for cancer therapy, Prior T cell receptor-engineered T cell therapy
I have HIV or active hepatitis B, or I've treated hepatitis with undetectable viral load.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Leukapheresis and Lymphodepletion
Subjects undergo leukapheresis to collect cells for manufacturing and a lymphodepleting regimen with cyclophosphamide and fludarabine, or bendamustine in preparation for cell infusion
2-3 weeks
Treatment
Cell infusion administered intravenously at a dose of 2.5 x 10^6 CAR+ cells/kg body weight
1 day
Follow-up
Participants are monitored for efficacy and safety outcomes, as well as health-related quality of life (HRQoL) for up to 2 years
2 years
Long-term Follow-up
Additional long-term follow-up conducted under a separate protocol
Participant Groups
The clinical trial is testing MB-CART2019.1 cells' effectiveness and safety in treating DLBCL that has resisted previous therapies. It's an open-label phase II study, meaning everyone gets the treatment and knows what it is, focusing on how well these cells work and their impact on patients.
1Treatment groups
Experimental Treatment
Group I: Single, open labelExperimental Treatment4 Interventions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Allegheny Health Network Cancer InstitutePittsburgh, PA
Georgia Cancer Center at Augusta UniversityAugusta, GA
Winship Cancer Institute of Emory UniversityAtlanta, GA
Mayo ClinicPhoenix, AZ
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Miltenyi Biomedicine GmbHLead Sponsor
References
[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.
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.
CAR T-cell therapy for B-cell lymphoma. [2022]Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.
Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non-Hodgkin lymphoma: A case report. [2021]Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.
Chimeric antigen receptor modified T cell therapy in B cell non-Hodgkin lymphomas. [2021]Chimeric antigen receptor modified T (CAR-T) cell therapy against the CD19 antigen has revolutionized the therapeutic landscape for patients with relapsed, refractory B cell non-Hodgkin lymphoma (NHL). Currently, there are two FDA approved products (axicabtagene ciloleucel and tisagenlecleucel) for B cell NHL, with several other constructs under clinical investigation. This review will focus on the clinical outcomes, toxicity profile, and differences among candidate CD19 CAR-T cell products for major subtypes of B cell NHL including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Lastly, we will describe novel CAR-T constructs currently under exploration in B cell NHL.
CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin's lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.
Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]Adoptive cellular immunotherapy with anti CD19 chimeric antigen receptor (CAR)-T cell has changed the treatment landscape in relapsed/refractory B cell lymphomas. They have emerged as effective therapy in patients with multiple relapsed/refractory disease, capable of sustaining durable remissions. Two CAR-T cell products (axicabtagene ciloleucel and tisagenlecleucel) are currently approved by the United States Food and Drug Administration. A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon. CAR-T cell-related toxicities, including infections, cytokine release syndrome, and neurotoxicity are potential complications of therapy. With increasing use of CAR-T cells, the mechanism of toxicities and mitigation strategies needs to be developed. Additionally, reasons for CAR-T cell failure and progression following this therapy needs to be further studied. We describe the recent developments in this field, with emphasis on the complications of therapy and factors contributing to toxicities, efficacy, and resistance. We also describe the ongoing research in this field and the newer CAR-T cell constructs that are being developed to counter the challenges that have been identified in this field.
Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. [2021]Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC025  = 4.24), neurological disorders (n = 963, IC025  = 2.42), hematological disorders (n = 532, IC025  = 3.32), infections (n = 287, IC025  = 2.38), cardiovascular disorders (n = 256, IC025  = 2.81), pulmonary disorders (n = 186, IC025  = 3.80), reno-metabolic disorders (n = 123, IC025  = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC025  = 5.01) and hepatic disorders (n = 32, IC025  = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.
Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.
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.