Relapsed/Refractory B-Cell Lymphoma
Conditions
Keywords
Relapsed/Refractory B-Cell Lymphoma, Nanobody, CD19, CD20, CAR-T
Brief summary
This is a single arm study to evaluate the safety and efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for Relapsed/Refractory B-Cell Lymphoma
Interventions
GENETICCD19/CD20 Tandem Dual CAR-T
Each subject will be infused with single dose of CD19/CD20 Tandem Dual CAR-T. A classic "3+3" dose escalation will be employed. The low dose is 2×10\^6 / kg, the medium dose is 4×10\^6 /kg, and the high dose is 6×10\^6 /kg.
Sponsors
Affiliated Hospital to Academy of Military Medical Sciences
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A classic "3+3" dose escalation will be employed. The starting dose is 2×10\^6 cells/kg, followed by sequential escalated doses of 4×10\^6 cells/kg and 6×10\^6 cells/kg.If no dose-limiting toxicity (DLT) is observed in 3 subjects at a given dose cohort, the study may proceed to the next higher dose level. Dose escalation will be discontinued if DLT occurs in 2 or more out of 3 subjects. If 1 DLT event occurs in the initial 3 subjects, another 3 subjects will be enrolled at the same dose. Escalation may continue if no DLT occurs in the supplementary 3 subjects. Dose escalation shall not proceed if DLT occurs in any of the additional subjects, or if a total of 2 or more DLT cases occur among 6 subjects in the same cohort.DLT refers to reasonably treatment-related toxic reactions within the DLT assessment window (Day 1 to Day 28 after CAR-T infusion), and toxicity grading shall comply with CTCAE 5.0.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subject has voluntarily signed the informed consent form with full consent, and is willing and able to comply with the scheduled visits, study treatments, laboratory tests, and other trial procedures 2. Patients with relapsed/refractory B-cell lymphoma confirmed by cytology or histology according to the WHO 2022 Classification: * Lymphoma cells confirmed to express CD19 and/or CD20 antigen by immunophenotyping or histopathological immunohistochemistry * B-cell lymphomas include: aggressive B-cell lymphomas (LBCL, BL, MCL) and indolent B-cell lymphomas (CLL/SLL, FL, MZL, LPL, HCL) * Relapsed/refractory B-cell lymphoma: For patients with aggressive lymphoma, disease stable for ≤12 months or disease progression after achieving best response following at least first- and second-line pharmacotherapy; or disease progression or relapse within ≤12 months after autologous stem cell transplantation. For patients with indolent lymphoma, disease progression, relapse or transformation following at least three lines of prior therapy 3. Aged 18-75 years (inclusive), male or female 4. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 5. Estimated overall survival of more than 3 months from the date of signing the informed consent form 6. Hemoglobin (HGB) ≥ 70 g/L (transfusion permitted) 7. Adequate hepatic, renal and cardiopulmonary function meeting the following criteria: * Creatinine ≤ 1.5 × ULN; * Left ventricular ejection fraction (LVEF) ≥ 50%; * Blood oxygen saturation \> 90%; * Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN 8. The subject agrees to use contraceptive measures from the date of signing the informed consent form until 1 year after CAR-T cell infusion
Exclusion criteria
* Severe cardiac insufficiency with left ventricular ejection fraction \< 50% * History of severe pulmonary function-impairing diseases * Concomitant other advanced malignant neoplasms * Concomitant severe infection that cannot be effectively controlled * Concomitant severe autoimmune diseases or congenital immunodeficiency disorders * Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA\] or hepatitis C virus ribonucleic acid \[HCV-RNA\] test result above the lower limit of detection) * Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection * History of severe allergy to biological products (including antibiotics) * Patients with allogeneic hematopoietic stem cell transplantation who still have acute graft-versus-host disease (GVHD) after one month of discontinuation of immunosuppressive agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| According to the incidence of treatment-related adverse events (AEs) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. | up to 3 years | Incidence of treatment-related adverse events (AEs) Description: Number and severity of adverse events graded according to CTCAE v5.0, including cytokine release syndrome (CRS) graded by ASTCT criteria and immune effector cell-associated neurotoxicity syndrome (ICANS) graded by ASBMT criteria |
| According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. | MTD will be determined based on DLTs observed during the first 28 days of study treatment | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| According to the objective response rate (ORR) to evaluate the efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. | Within 3 months following infusion of CD19/CD20 Tandem Dual CAR-T | Overall Response Rate (ORR) Description:For B-cell lymphoma, ORR is defined according to the Lugano Classification for Lymphoma Response Assessment. ORR represents the proportion of patients achieving complete response (CR) or partial response (PR). |
Contacts
CONTACTYamei Wu
Outcome results
None listed