A Prospective, Open-Label, Multicenter, Randomized Controlled Study Comparing the Efficacy and Safety of Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Combined With Orelabrutinib/Chidamide/Venetoclax/Lenalidomide/PD1 (Pola-RCHP-X) Versus RCHOP-X and Pola-RCHP in Previously Untreated Patients With Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 528
- 主要终点
- Progression Free Survival at 24 months (PFS24) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma
研究概览
简要总结
This study aims to compare the efficacy and safety of Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone combined with Orelabrutinib/Chidamide/Venetoclax/Lenalidomide/PD1 (Pola-RCHP-X) versus RCHOP-X and Pola-RCHP in previously untreated patients with DLBCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign the informed consent form
- •Previously untreated participants with CD20-positive DLBCL
- •Life expectancy ≥ 6 months
- •IPI score 2-5
- •ECOG Performance Status of 0, 1, or 2
- •Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
- •Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to involvement of the spleen by DLBCL per the investigator for which blood product transfusions are permitted) defined as follows:
- •Hemoglobin ≥ 9.0 g/dL without packed RBC transfusion during 7 days before first treatment ANC ≥ 1.0 x 10^9/L PLT ≥ 75 x 10^9/L
排除标准
- •Contraindication to any of the individual components of Pola-RCHP or Orelabrutinib/Chidamide/Venetoclax/Lenalidomide/PD1
- •History of other malignancy that could affect compliance with the protocol or interpretation of results
- •Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina
- •History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
- •Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
- •Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):
- •Serum AST and ALT ≥ 2.5 x ULN Total bilirubin ≥ 1.5 x ULN Serum creatinine clearance < 40 mL/min (using Cockcroft-Gault formula)
- •Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
- •Participants with a history of progressive multifocal leukoencephalopathy
研究组 & 干预措施
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Polatuzumab vedotin (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Rituximab (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Cyclophosphamide (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Doxorubicin (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Prednisone (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Orelabrutinib (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Venetoclax (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Chidamide (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Penpulimab (Drug)
Pola-RCHP-X
From cycles 1 to 6, patients will receive Polatuzumab Vedotin 1.8 mg/kg, Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², and Doxorubicin 50 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Lenalidomide (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Rituximab (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Cyclophosphamide (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Doxorubicin (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Vincristine (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Prednisone (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Orelabrutinib (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Venetoclax (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Chidamide (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Penpulimab (Drug)
RCHOP-X
From cycles 1 to 6, patients will receive Rituximab 375 mg/m², Cyclophosphamide 750 mg/m², Doxorubicin 50 mg/m², and Vincristine 1.4 mg/m² on day 1 of each cycle, and Prednisone 100 mg/day from days 1 to 5. From cycles 2 to 6, patients will receive either Orelabrutinib 150 mg/day (days 1-21), Venetoclax 800 mg (days 4-10 in cycle 2; days 1-10 in cycles 3-6), Chidamide 20 mg/day (days 1, 4, 8, 11), Penpulimab 200 mg/day (day 0), or Lenalidomide 25 mg/day (days 1-10). In cycles 7 to 8, patients will receive Rituximab 375 mg/m² on day 1 of each cycle.
干预措施: Lenalidomide (Drug)
Pola-RCHP
From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.
干预措施: Polatuzumab vedotin (Drug)
Pola-RCHP
From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.
干预措施: Rituximab (Drug)
Pola-RCHP
From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.
干预措施: Cyclophosphamide (Drug)
Pola-RCHP
From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.
干预措施: Doxorubicin (Drug)
Pola-RCHP
From cycles 1 to 6, patients will receive Polatuzumab Vedotin at 1.8 mg/kg, Rituximab at 375 mg/m², Cyclophosphamide at 750 mg/m², and Doxorubicin at 50 mg/m² on day 1 of each cycle, and Prednisone at 100 mg/day from days 1 to 5. In cycles 7 to 8, patients will receive Rituximab at 375 mg/m² on day 1 of each cycle.
干预措施: Prednisone (Drug)
结局指标
主要结局
Progression Free Survival at 24 months (PFS24) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma
时间窗: At 24 months
次要结局
- Overall Survival (OS)(up to approximately 48 months)
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(From enrollment to study completion, a maximum of 48 months)
- Complete Response Rate (CRR) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma(End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days])
- Overall Response Rate (ORR) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma(End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 8 [Cycle length=21 days])
- Event Free Survival (EFS) Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma(up to approximately 48 months)
研究者
WEI XU
M.D
The First Affiliated Hospital with Nanjing Medical University