[Translation] A phase I clinical trial study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of ZXBT-1158 capsules in the treatment of advanced relapsed and refractory B-cell malignancies
Ia剂量递增阶段主要目的:评价ZXBT-1158胶囊治疗晚期复发难治B细胞恶性肿瘤的耐受性和安全性,确定MTD。次要目的:评价ZXBT-1158胶囊治疗晚期复发难治B细胞恶性肿瘤的初步疗效;评价单次和多次口服ZXBT-1158胶囊在复发难治B细胞恶性肿瘤患者中的人体药代动力学(PK)特征;评估ZXBT-1158胶囊对外周血单个核细胞(PBMCs)中BTK的抑制程度。
Ib剂量扩展阶段主要目的:评价ZXBT-1158胶囊治疗复发难治外周B细胞恶性肿瘤、原发或继发中枢神经系统淋巴瘤的安全性和剂量耐受性,并确定RP2D。次要目的:进一步评价ZXBT-1158胶囊治疗复发难治外周B细胞恶性肿瘤、原发或继发中枢神经系统淋巴瘤的初步疗效;评价单次和多次口服ZXBT-1158胶囊在复发难治外周B细胞恶性肿瘤、原发或继发中枢神经系统淋巴瘤患者中的人体药代动力学(PK)特征;评估ZXBT-1158胶囊对外周血单个核细胞(PBMCs)中BTK的抑制程度。
探索型目的:探索原发或继发中枢神经系统淋巴瘤患者的脑脊液中ZXBT-1158的浓度。
[Translation] The main purpose of the Ia dose escalation phase: to evaluate the tolerability and safety of ZXBT-1158 capsules in the treatment of advanced relapsed and refractory B-cell malignancies, and to determine the MTD. Secondary objectives: To evaluate the preliminary efficacy of ZXBT-1158 capsules in the treatment of advanced relapsed and refractory B-cell malignancies; to evaluate the human pharmacokinetics of single and multiple oral administration of ZXBT-1158 capsules in patients with relapsed and refractory B-cell malignancies ( PK) characteristics; to evaluate the degree of inhibition of BTK in peripheral blood mononuclear cells (PBMCs) by ZXBT-1158 capsules.
Main objective of dose expansion phase Ib: To evaluate the safety and dose tolerability of ZXBT-1158 capsules in the treatment of relapsed and refractory peripheral B-cell malignancies, primary or secondary central nervous system lymphoma, and to determine RP2D. Secondary objective: To further evaluate the preliminary efficacy of ZXBT-1158 capsules in the treatment of relapsed and refractory peripheral B-cell malignancies, primary or secondary central nervous system lymphoma; Human pharmacokinetic (PK) profile in patients with B-cell malignancies, primary or secondary central nervous system lymphoma; evaluation of the degree of inhibition of BTK in peripheral blood mononuclear cells (PBMCs) by ZXBT-1158 capsules.
Exploratory purpose: To explore the concentration of ZXBT-1158 in the cerebrospinal fluid of patients with primary or secondary central nervous system lymphoma.