relapsed or refractory CD20-positive B-cell Non-Hodgkin's lymphoma
Conditions
Interventions
experimental group1:5mg/m2
experimental group3:20 mg/m2
experimental group2:10 mg/m2
experimental group4:30 mg/m2
experimental group5:40 mg/m2
experimental group6:50 mg/m2
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1) Patient has the ability and willingness to be performed follow-up per protocol and has signed/ signed a written informed consent form by the legal representative. 2) Aged 18 to 70 years, male or female; 3) Pathologically confirmed CD20 + relapsed or refractory B-cell Non-Hodgkin lymphoma: the types included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL); 4) The first dose was at least 4 weeks after the last anti-tumor chemotherapy and radiotherapy; biotherapeutic and immunotherapy washout period >= 4 weeks; 5) Toxicities due to any prior therapy, surgery, or radiation therapy must have recovered to NCI-CTCAE v5.0 grade = 1.5 cm; 7) Measured/ predicted value of vital capacity (VC)>= 60%, or diffusing function of carbon monoxide (DLCO) >= 50% predicted value; 8) Blood routine examination: WBC >= 3x10^9/ L, Hgb>=75 g/ L, ANC >=1.5x10^9/ L, PLT >=75x10^9/ L; 9) Hepatic and renal function: BUN and Cr <= 2 times the upper limit of normal, ALT and AST <= 3 times the upper limit of normal, and TBIL <= 2 times the upper limit of normal; 10) Before enrollment, in the absence of anticoagulant therapy, coagulation function: the International Normalized Ratio (INR) is <= 1.5x ULN, and the activated partial thromboplastin time (APTT) is <= 1.5 ULN; 11) The ECOG score: 0-1; 12) The expected survival time is greater than 3 months.
Exclusion criteria
Exclusion criteria: 1) Taken Rituximab within 3 months before the first administration; 2) Rituximab ADA positive in peripheral blood at screening; 3) The residual concentration of Rituximab in peripheral blood at screening is >24 ug/ mL; 4) Definite drug allergy history, allergy history of foreign protein, biological agent or ingredients of investigational drug; 5) Results of anti-HIV (+) or anti-HCV (+) or HBsAg (+) or combined with HBV-DNA quantification above the upper limit of detection; 6) Infiltrative diseases of central nervous system tumors; 7) Combined with peripheral or central nervous system disorders; 8) Diabetes mellitus not be controlled by medical treatment as assessed by the investigator; 9) Patients with other malignant tumors within the past 5 years; 10) Combined with active autoimmune disease (e.g. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, etc.) 11) Combined with severe cardiovascular disease as follows, a) Myocardial infarction within the past 6 months during the screening period; b) Unstable angina pectoris during the screening period of nearly 3 months; c) Cardiac insufficiency (cardiac functional class >= NYHA standard class II); d) Severe arrhythmia (e.g., sustained ventricular tachycardia, ventricular fibrillation); e) QTc prolongation (450 msec in males and 470 msec in females); f) Grade II or Grade III heart block; g) Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) 12) Combined with other serious diseases, serious active infection, such as pneumonia, active pulmonary tuberculosis, interstitial lung disease, etc.; 13) Treatment with hematopoietic growth factors including colony stimulating factors, interleukin or blood transfusion within 1 week prior to the first dose; 14) Administration of steroids (equivalent amount of prednisone) greater than 20 mg/ day for more than 14 consecutive days or immunosuppressive therapy within 1 month prior to the first dose; 15) Received all kinds of vaccines within 1 month before the first administration; 16) Major surgery within 1 month prior to first dose (except for diagnostic biopsy); 17) Patients who have received autologous stem cell transplantation within 3 months prior to the start of the study; 18) Patients who have received allogeneic stem cell transplantation; 19) Patients with Grade >= 3 infusion reactions after previous treatment with monoclonal antibodies; 20) Patients with CD20 + relapsed or refractory B-cell non-Hodgkin lymphoma by histological transformation (Richter) [types include diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL)]; 21) Pregnant/ lactating women, or male or female patients of childbearing potential who are unwilling to use effective contraception during the trial and for 6 months after the last dose; 22) Participation in a recent clinical trial of another drug or medical device with a last treatment period of less than 4 weeks prior to the first dose, or planning to participate in any other clinical trial during the course of this study. 23) Patients previously treated with CAR-T. 24) Other situations that are not suitable for the enrollment thought by investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MTD;RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of CD20 + cells in peripheral blood of patients at different time points;Pharmacokinetic parameters: Evaluation indicators: TRS005, serum concentration of total antibody and MMAE. Single dose: Cmax, Tmax, t1/2, AUC0-8, AUC0-t, CL, etc. Multiple dose: Cmax,ss, Cmin,ss, Tmax,ss, t1/2, AUC0-t,ss, degree of fluctuation, fluctuation coefficient, etc.;ADA;ORR; | — |
Countries
China
Contacts
Public ContactShi Yuankai
National Cancer Center /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed