View clinical trials related to Leukemia, B-Cell.
Filter by:Immunotherapy offers an extremely precise approach with the potential to eliminate cancer cells specifically. The newly designed CD19 targeted ICAR19 T cells can specifically kill CD19+ tumor cells. ICAR19 CART used the second generation of CART designation. In this study, the participants will receive several doses of autologous ICAR19 T cells and the investigators will determine the safety and therapeutic effects of these cells.
Autologous T cells engineered to express chimeric antigen receptors (CARs) against leukemia antigens such as CD19 on B cells have shown promising results for the treatment of relapsed or refractory B-cell malignancies. However, a subset of cancer patients especially heavily pretreated cancer patients could be unable to receive this highly active therapy because of failed expansion. Moreover, it is still a challenge to manufacture an effective therapeutic product for infant cancer patients due to their small blood volume. On the other hand, the inherent characters of autologous CAR-T cell therapy including personalized autologous T cell manufacturing and widely "distributed" approach result in the difficulty of industrialization of autologous CAR-T cell therapy. Universal CD19-specific CAR-T cell(UCART019),derived from one or more healthy unrelated donors but could avoid graft-versus-host-disease (GVHD) and minimize their immunogenicity, is undoubtedly an alternative option to address above-mentioned issues. We have generated gene-disrupted allogeneic CD19-directed BBζ CAR-T cells (termed UCART019) by combining the lentiviral delivery of CAR and CRISPR RNA electroporation to disrupt endogenous TCR and B2M genes simultaneously and will test whether it can evade host-mediated immunity and deliver antileukemic effects without GVHD. The main goal of the phase 1 portion of this phase 1/2 trial is to evaluate the safety and tolerability of several doses of UCART019 in patients with relapsed or refractory CD19+ leukemia and lymphoma, so as to establish the recommended dose and/or schedule of UCART019 for phase 2 portion. The recommended Phase 2 dose will be defined as the highest dose level of UCART019 that induced DLT in fewer than 33% of patients (i.e., one dose level below that which induced DLT in at least two of six patients). Phase 2 portion of the trial will not be initiated until the recommended Phase 2 dose is determined. In the phase 2 portion of this trial, we will mainly determine if UCART019 help the body's immune system eliminate malignant B-cells. Safety of UCART019 and impact of this treatment on survival will also be observed.
A chimeric antigen receptor gene-modified T cells (CART: 4SCAR19)by targeted the CD19 (cluster of differentiation antigen 19), treat patients with CD19 positive malignant B cells tumor, assess treatment safety, and observe therapeutic effects. At the same time,the change process of the CART and residual tumor status of the patient are observe dynamically， which summarizes the best therapeutic effect.
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell malignancy including lymphoma or leukemia.
This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with (1) high risk, relapsed/refractory (r/r) CD19+ B-ALL; (2) r/r DLBCL; (3) r/r CLL/SLL and (4) r/r FL and (5) r/r MCL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with the lentiviral pCCL.PGK.alpha.CD19CAT-41BBzeta vector, CD19CAT-41BBζ CAR T-cells (referred to subsequently as CD19CAR T-cells) which is classified as a gene therapy medicinal product. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP. The ATIMP will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL, DLBCL, B-CLL/SLL, FL and MCL. Recruitment into the ALL cohort has been completed and no further patients with ALL are being treated on the study. Patients receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only will also receive a single dose of pembrolizumab 200 mg at day -1. Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area. - Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10^6 CD19 CAR T-cells and a possible second dose of 310 x 106 CAR T-cells - Regimen A2: Patients with B-ALL with a baseline marrow blast% of >20% receive a split dose with a first dose of 10 x 10^6 CD19CAR T-cells and a possible second dose of 400 x 10^6 CAR T-cells - Regimen B: Patients with DLBCL receive a single dose of 200 x 10^6 CAR T-cells - Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 106 CD19 CAR T-cells and a possible second dose of 200 x 10^6 CD19 CAR T-cells. - Regimen D: Patients with FL and MCL receive a single dose of 200 x 10^6 CAR T-cells The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells. After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, enter long term follow up until 10 years post-CD19CAR T-cell infusion.
This single arm, open-label, multi-center clinical trial is studying CD19 targeted chimeric antigen receptor T cells therapy in treating patients with CD19 positive malignant B-cell derived leukemia and lymphoma that is relapsed (after stem cell transplantation or chemotherapy) or refractory to chemotherapy.
In the conventional treatment options, B cell leukemia could be treated with chemotherapy drugs or HSCT. But chemotherapy could barely cured leukemia. And HSCT is often limited by lacking of HLA-matched donors, even if those patients who received HSCT still could be relapsed. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with relapsed or refractory B cell leukemia, including relapsed cases after HSCT. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells. At the same time, evaluating the possible and clinical responses of using donor-derived T cells engineered CAR-T cells. Detailed Description: This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator. And optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. The source of T cells for CAR-T is from two aspects, one is autologous, the other is donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depend on the situation of individual CAR-T cells preparation.
This is a single center, single arm, open-label pilot study to determine the feasibility and safety of a single dose administered as spilt fractions of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART22" cells) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Objectives: The purpose of this study is to evaluate the safety and prognosis of New Cluster of Differentiation Antigen 19-chimeric Antigen Receptor T (nCAR19-T) Cells in the treatment of recurrent/refractory B-cell tumor and the Optimal dosage of nCAR19-T cell therapy. Methods: This study designs a novel therapy using nCAR19-T. 20 patients will be enrolled. Cyclophosphamide 500 mg - 2000 mg/m2 (day 2) with or without Fludarabine 30 mg/m2 /day, 4 days (day-6,-5,-4,-3); nCAR19-T transfusion：day 0(5×10※5/kg，1×10※6/kg，3×10※6/kg). According to the National Cancer Institute (NCI) standard (CTCAE), they will be observed 24 weeks long. Follow-up survey after the clinical study: within 1 months, once a week; then once a month for 1 years; and then once a year, a total of 15 years.