A Study of Pirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin (Pirto-R-GemOx±Pola) in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- complete response rate(CRR)
研究概览
简要总结
This is a prospective, single arm trial in patients with ≥ 18 years with relapsed and refractory DLBCL. Aim of this study is to evaluate the efficacy and safety of pirtobrutinib in combination with rituximab, gemcitabine, and oxaliplatin with or without polatuzumab vedotin (Pirto-R-GemOx±pola) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) previously treated with covalent BTK inhibitors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed DLBCL (2016 WHO criteria) of MCD, BN2, N1 subtypes, double-expressor, intravascular large B-cell lymphoma, or other BTK-sensitive subtypes
- •Disease progression/relapse after covalent BTK inhibitor therapy
- •≥1 measurable lesion (nodal >15mm/extranodal >10mm) on PET/CT within 28 days
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •age ≥18 years
- •Adequate organ function:
- •ANC ≥0.5×10⁹/L ；Platelets ≥50×10⁹/L (transfusion-independent)；Bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN；Cr ≤1.5×ULN or CrCl ≥30mL/min；LVEF ≥50% (NYHA class <III)
- •Life expectancy >3 months
- •Sign the written ICF, and be able to comply with the visits and related procedures stipulated in the protocol;
- •Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last treatment.
排除标准
- •DLBCL with central nervous system (CNS) or meningeal involvement
- •Histologically transformed DLBCL
- •Contraindications or hypersensitivity to any drug in the combination regimen
- •Major surgery within 4 weeks prior to treatment (excluding vascular access placement or biopsy)
- •Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or compliance with study procedures
- •Poorly controlled cardiac clinical symptoms or diseases, including:
- •i. NYHA Class II or higher heart failure ii. Unstable angina iii. Myocardial infarction within 1 year iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment/intervention
- •Active hemorrhage
- •Poorly controlled systemic bacterial, viral, fungal, or parasitic infections (excluding fungal nail infections), or other clinically significant active diseases that render patients unsuitable for trial participation per investigator assessment
- •Patients with:Active chronic hepatitis B or C.Positive HBsAg and/or HBcAb or HCV antibodies at screening must demonstrate HBV DNA ≤2,500 copies/mL (or 500 IU/mL) to exclude active HBV/HCV infection requiring treatment.HBsAg/HBcAb-positive patients must receive antiviral prophylaxis.
- •HIV-infected patients and/or AIDS patients
- •Inability to swallow tablets, malabsorption syndrome, or any gastrointestinal disorder/ dysfunction that may impair drug absorption
- •Lactating or pregnant women
- •Psychiatric disorders or inability to provide informed consent
- •Any other condition deemed unsuitable for study participation by the investigator
研究组 & 干预措施
pirtobrutinib+R-GemOx with or without polatuzumab vedotin
DLBCL patients will receive Pirto-R-GemOx for a total of 6 treatment cycles (21days per cycle). Patient who is CD79b positive and has not previously received polatuzumab Vedotin will combine with polatuzumab Vedotin.The efficacy will be evaluated every 3 cycles, young patients with CR will receive ASCT, CR patients who do not undergo ASCT or PR patients will continued for 3 cycles.If the efficacy is evaluated as CR or PR after 6 cycles, then ASCT for young patients, and lenalidomide maintenance treatment for elderly patients for 2 years (25mg, day 1-21, Q4W). ctDNA testing will be performed at baseline、before the second course、and at the end of treatment.
干预措施: Pirtobrutinib (Drug)
pirtobrutinib+R-GemOx with or without polatuzumab vedotin
DLBCL patients will receive Pirto-R-GemOx for a total of 6 treatment cycles (21days per cycle). Patient who is CD79b positive and has not previously received polatuzumab Vedotin will combine with polatuzumab Vedotin.The efficacy will be evaluated every 3 cycles, young patients with CR will receive ASCT, CR patients who do not undergo ASCT or PR patients will continued for 3 cycles.If the efficacy is evaluated as CR or PR after 6 cycles, then ASCT for young patients, and lenalidomide maintenance treatment for elderly patients for 2 years (25mg, day 1-21, Q4W). ctDNA testing will be performed at baseline、before the second course、and at the end of treatment.
干预措施: R-GemOx (Drug)
pirtobrutinib+R-GemOx with or without polatuzumab vedotin
DLBCL patients will receive Pirto-R-GemOx for a total of 6 treatment cycles (21days per cycle). Patient who is CD79b positive and has not previously received polatuzumab Vedotin will combine with polatuzumab Vedotin.The efficacy will be evaluated every 3 cycles, young patients with CR will receive ASCT, CR patients who do not undergo ASCT or PR patients will continued for 3 cycles.If the efficacy is evaluated as CR or PR after 6 cycles, then ASCT for young patients, and lenalidomide maintenance treatment for elderly patients for 2 years (25mg, day 1-21, Q4W). ctDNA testing will be performed at baseline、before the second course、and at the end of treatment.
干预措施: Polatuzumab Vedotin (Drug)
结局指标
主要结局
complete response rate(CRR)
时间窗: Up to 6 cycles (each cycle is 21 days)
CRR after treated by pirto-R-GemOx±pola
次要结局
- Progression-free survival (PFS)(Up to 6 cycles (each cycle is 21 days))
- Overall Survival (OS)(up to 6 cycles(each cycle is 21 days))
- undetectable MRD rate(Up to 6 cycles (each cycle is 21 days) ± pola)
- Objective response rate(ORR)(Up to 6 cycles (each cycle is 21 days) ± pola)
研究者
Zhao Weili
First Deputy Director of Shanghai Institute of Hematology
Ruijin Hospital