Open-Label, Dose Escalation/Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and/or High-Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Gene Rearrangements
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 9
- 主要终点
- Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation Phase (Part 1)
Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: RO6870810 (Drug)
Dose Escalation Phase (Part 1)
Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: Venetoclax (Drug)
Dose Escalation Phase (Part 1)
Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: Rituximab (Drug)
Expansion Phase (Part 2)
Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: RO6870810 (Drug)
Expansion Phase (Part 2)
Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: Venetoclax (Drug)
Expansion Phase (Part 2)
Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death.
干预措施: Rituximab (Drug)
结局指标
主要结局
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1
时间窗: Up to 36 months
Complete Response (CR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- Recommended Dose (RD) Expansion - Part 2
时间窗: Up to 36 months
Percentage of Participants With Adverse Events (AEs) - Part 1
时间窗: Up to 36 months
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Overall Response (OR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- RD Expansion - Part 2
时间窗: Up to 36 months
Percentage of Participants With Dose-Limiting Toxiciities (DLT)- Part 1
时间窗: Cycle (C) 1 (21 days)
DLT is defined as any of the toxicities- occurs within the first cycle for which the participant receives the full intended combination doses and number of administrations; is considered to be related to study treatment by the investigator; is not attributed to disease progression or another clearly identifiable cause.
次要结局
- Duration of Response (DoR)- Part 1 and Part 2(Up to 36 months)
- Progression-Free Survival (PFS)- Part 1 and Part 2(Up to 36 months)
- Event-Free Survival (EFS)- Part 1 and Part 2(Up to 36 months)
- Disease-Free Survival (DFS)- Part 1 and Part 2(Up to 36 months)
- Percentage of Participants With Adverse Events (AEs) - Part 2(Up to 36 months)
- Trough Serum Concentration (Cmin) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Cycle 2 and all other subsequent even Cycles (Up to 36 months))
- Clearance (CL) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))
- Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of Modified Lugano Response Criteria- Part 1 and Part 2(Up to 36 months)
- Time of Maximum Concentration (tmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))
- Overall Survival (OS)- Part 1 and Part 2(Up to 36 months)
- Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 2(Up to 36 months)
- Maximum Concentration (Cmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))
- Volume of Distribution (Vd) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))
- Complete Response (CR) Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2(Up to 36 months)
- Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2(Up to 36 months)
- Complete Response (CR) Rate as Determined by the Investigator Based on the Modified Lugano Response Criteria- Part 1 and Part 2(Up to 36 months)
- Percentage of Ant-Drug Antibodies (ADA) Against Rituximab - Part 1 and Part 2(Pre-dose, End of Infusion Day 1 Cycle 1; Pre-dose Day 1 Cycle 2, 3, 4 , 6 and all other even Cycles (Up to 36 months))
- Area Under the Curve (AUC) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))
- Half-Life (t1/2) of RO6870810 and its Potential Metabolites- Part 1 and Part 2(Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months))