Refractory or Relapsed Aggressive B-cell Non-Hodgkin Lymphoma
Conditions
Interventions
CART group:infusion of 4×10^6 CAR+ cells/kg
Sponsors
Department of Hematology, Institute of Hematology, Changhai Hospital, Naval Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Sign the informed consent form, and be willing and able to comply with the visit, treatment protocols, laboratory tests, and other requirements specified in the trial protocol. 2. Age = 18 years, regardless of gender. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. 4. Expected life-span = 3 months. 5. Diagnosed CD19-positive r/r B-NHL patients: - Patients diagnosed with DLBCL (including FL with DLBCL, FL transformed into DLBCL, non-specific subtypes of DLBCL, and specific subtypes such as PMBCL) based on the WHO 2016 criteria, 3b FL patients, and high-grade B-cell lymphoma (DHL/THL/NOS) patients. - Patients who have received standardized first-line treatment and at least 2 courses of second-line treatment (excluding those who relapsed after stem cell transplantation) and have previously used CD20-targeted drugs and anthracycline drugs. - The definition of relapsed or refractory (according to the NCCN guidelines for B-cell lymphoma (2020.V4)) includes at least one of the following: a. Relapse or progression after hematopoietic stem cell transplantation (SCT), entering the transplantation relapse sequence. b. Evaluation as SD/PD after at least second-line treatment, classified as the refractory cohort after second-line treatment. c. Recurrence after CR evaluation after at least second-line treatment, classified as the relapse cohort after second-line treatment. d. For low-grade lymphomas that have transformed into high-grade lymphomas (including FL transformed into DLBCL), evaluation of SD/PD after at least first-line treatment, classified as the refractory cohort after second-line treatment. e. For low-grade lymphomas that have transformed into high-grade lymphomas (including FL transformed into DLBCL), recurrence after CR evaluation after at least first-line treatment,classified as the relapse sequence after second-line treatment. 6. At least one measurable lesion (according to the Lugano 2014 criteria) as the evaluation basis. For intra-nodal lesions, the long diameter should be = 1.5 cm and the short diameter should be = 1.0 cm. For extra-nodal lesions, the long diameter should be = 1.0 cm. (The imaging testing data within 30 days prior to obtaining informed consent during the screening period should be provided, and no other anti-tumor treatment should have been received during this period). 7. The function of important organs must meet the following criteria: a. Serum creatinine = 1.5 times the upper limit of normal (ULN). b. ALT and AST = 2.5 ULN; total bilirubin = 1.5 ULN. c. Hemodynamically stable with a left ventricular ejection fraction (LVEF) = 50%. d. Hemoglobin = 90 g/L; platelet count = 75 × 10^9/L; absolute neutrophil count (ANC) = 1.0 × 10^9/L. e. The minimum reserve of pulmonary function is required (dyspea not higher than grade 1 (according to CTCAE 5.0 criteria) and arterial oxygen saturation > 91% under indoor conditions). 8. Male patients with reproductive ability or female patients with the possibility of pregnancy must meet one of the following criteria: a. Surgically sterile. b. Female patients with menopause = 2 years or negative serum pregnancy test during the screening period. c. Agree to use highly effective contraception methods such as oral contraceptives, intrauterine devices, or barrier methods combined with spermicides within 2 years from screening to cell infusion. Candidates who do not meet any of the above con
Exclusion criteria
Exclusion criteria: 1. Patients with a history of malignancies other than the target indication within the past 2 years, excluding patients who received curative treatment and had no recurrence of malignancy over 2 years (excluding patients with non-melanoma skin cancer, basal cell or squamous cell carcinoma of the skin, localized prostate cancer, ductal carcinoma in situ, papillary or follicular thyroid cancer, patients with lymphoma transformed to invasive lymphoma, and patients with carcinoma in situ). 2. Patients with Richter's syndrome and patients diagnosed with leukemia. 3. Patients who have undergone autologous hematopoietic stem cell transplantation within the previous 6 weeks. 4. Patients who have received targeted therapy against CD19, CAR-T therapy, or other gene-modified T cell therapy. 5. Patients who have received antibody therapy (including anti-CD20 antibodies), radiation therapy, or chemotherapy within the previous 2 weeks. 6. Patients who have undergone major surgery within the previous 4 weeks or are planned to undergo surgery during the study. 7. Patients with active hepatitis B (HBV-DNA copies/ml > 105, HBsAg and HBcAb can be exempted from HBV-DNA testing if both are negative), active hepatitis C (HCV-RNA copies/ml > ULN, HCV antibody negative can be exempted from HCV-RNA testing), HIV infection (HIV-RNA positive or antibody positive), and Treponema pallidum infection (positive TP antibody). 8. Central nervous system (CNS) lymphoma, NHL with brain metastasis, or malignant tumor cells detected in cerebrospinal fluid. 9. Patients with severe underlying diseases that may limit their participation in the clinical trial, as determined by the investigator, including but not limited to severe immunosuppression, poorly controlled diabetes, gastric ulcers, active autoimmune diseases, deep venous thrombosis, and pulmonary embolism. 10. Patients with severe heart disease, including but not limited to New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, poorly controlled angina or arrhythmias, poorly controlled hypertension, hypotension, or severe cardiovascular disease. 11. Patients with poorly controlled systemic fungal, bacterial, viral, or other infections at screening. 12. Patients who have participated in other drug clinical trials within the previous 30 days before screening or are planned to participate in other drug clinical trials during the study. 13. Patients receiving or have received high-dose (60 mg dexamethasone or an equivalent dose of other systemic glucocorticoids) systemic glucocorticoid therapy within the previous 2 weeks before enrollment, or subjects who, in the opinion of the investigator, require long-term use of systemic steroids during the study (excluding topical use, inhalation use, or physiological replacement therapy for adrenal insufficiency with standard doses of glucocorticoids). 14. Patients with a known allergy or a history of allergic reactions to the study drug (including HD CD19 CAR-T, cyclophosphamide, and fludarabine. 15. Any other medical conditions that may interfere with the safety and efficacy assessment of the investigational drug in this study. 16. Pregnant and lactating women. 17. Other situations deemed unsuitable for enrollment by the investigators. Individuals meeting any of the above conditions are not eligible to be selected as participants.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the lesion of lymphoma;time of CART survival in vivo;level of CART expansion; | — |
Secondary
| Measure | Time frame |
|---|---|
| time of survival; | — |
Countries
China
Contacts
Public ContactJianmin Yang
Department of Hematology, Institute of Hematology, Changhai Hospital, Naval Medical University
Outcome results
None listed