Phase Ib/II Study of Toripalimab In Combination With Rituximab Followed by R-CHOP Regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) for Elderly Naïve Patients With Diffuse Large B-cell Lymphoma
1. Phase I portion of this study will evaluate the efficacy and saftey of toripalimab plus rituximab in treating untreated elderly diffuse large B cell lymphoma patients. 2. The aim of phase II portion of this study will evaluate the efficacy and saftey of toripalimab plus rituximab followed by R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen in treating untreated elderly diffuse large B cell lymphoma patients.
• Volunteer to participate in clinical research; fully understand and know the research and sign the Informed Consent Form (ICF); willing to follow and have the ability to complete all trial procedures;
• Aged 60-75 years old male or female;
• Untreated,without any anti-lymphoma treatment;
• DLBCL, or follicular lymphoma grade 3B, or transformed DLBCL, EBV (+) DLBCL, ALK (+) DLBCL, high-grade lymphoma were confirmed by histopathology examination;
• Clinical stage II-IV, or stage I with bulky diesase (diameter \> 7.5 cm);
• International Prognostic Score (IPI): 2-5;
• Paraffin tissue specimens or fresh puncture tissue specimens are available;
• Eastern cooperative oncology group score: 0-2;
• Estimated survival ≥ 12 months;
⁃ There must be at least one evaluate able or measurable lesion that meets the Lugano 2014 Lymphoma criteria \[evaluable lesion: 18F-fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) examination showing increased lymph node or extranodal uptake (higher than liver) and PET and/or computed tomography (Computed Tomography) CT) features are consistent with lymphoma findings; lesions can be measured: nodular lesions \> 15mm or extranodal lesions \> 10mm (if the only measurable lesion has received radiotherapy in the past, there must be evidence of radiological progress after radiotherapy), and accompanied by increased 18FDG uptake). Except for this, there is no measurable increase in diffuse 18FDG uptake in the liver;
⁃ Adequate organ and bone marrow function, no severe hematopoietic dysfunction, cardiac, pulmonary, liver, kidney, thyroid dysfunction and immune deficiency (no blood transfusion, granulocyte colony stimulating factor or other medical support was received within 14 days prior to the use of the research drug): 1) The absolute value of neutrophils (\>1.5×10\^9/L); 2) platelet count (\> 75×10\^9/L); 3) Hemoglobin (\> 9 g/dL); 4) Upper Limit Normal (ULN) or creatinine clearance rate (\>40 mL/min) of serum creatinine (\<1.5 times normal value upper limit) (estimated by Cockcroft-Gault formula); 5) Serum total bilirubin \< 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) = 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR) = 1.5 times ULN; Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) = 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are using anticoagulant therapy at screening time). Within the expected range; 8) Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (+10%);
⁃ There was no evidence that subjects had difficulty breathing at rest, and the measured value of pulse oximetry at rest was more than 92%;
⁃ Participants must pass a pulmonary function test (PFT) to confirm that forced expiratory volume (FEV1)/forced vital capacity (FVC) in the first second is more than 60%, unless it is a large mediastinal mass caused by lymphoma that cannot meet this standard; carbon monoxide diffusion (DLCO), FEV1 and FVC are all above 50% of the predicted value; all PFT results must be obtained within four weeks before the first administration;
⁃ Women of Childbearing Potential (WOBCP) must undergo a serum pregnancy test within seven days before the first medication and the results are negative. WOBCP or men and their WOBCP partners should agree to take effective contraceptive measures from the signing of ICF until six months after the last dose of the research drug is used.