A Phase Ib Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Venetoclax in Combination With Polatuzumab Vedotin Plus Rituximab (R) and Cyclophosphamide, Doxorubicin, Prednisone (CHP) in Patients With Untreated BCL-2 Immunohistochemistry (IHC)-Positive Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 20
- 主要终点
- Percentage of Participants with Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This Phase Ib, open-label, multicenter study evaluates the safety, efficacy, and pharmacokinetics of venetoclax in combination with Pola + R-CHP in previously untreated participants with BCL-2 IHC-positive DLBCL. Approximately 50 participants will be enrolled in this study in five consecutive cohorts each consisting of approximately 10 participants.
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
- •Previously untreated participants with CD20-positive DLBCL.
- •BCL-2 protein overexpression by IHC, as assessed by local testing.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or
- •International Prognostic Index (IPI) 2-
- •Life expectancy of more than 6 months.
- •Left ventricular ejection fraction (LVEF) ≥ 50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO).
- •Availability of archival or freshly collected tumor tissue prior to study enrollment.
- •At least one bi-dimensionally fluorodeoxyglucose-avid measurable lymphoma lesion on PET/CT scan, defined as > 1.5 cm in its longest dimension on CT scan.
- •Adequate hematopoietic function.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
排除标准
- •Current diagnosis of unclassifiable B-cell lymphoma.
- •Prior treatment for indolent lymphoma.
- •Current Grade > 1 peripheral neuropathy.
- •Prior organ transplantation.
- •Prior use of any monoclonal antibody within 3 months and any investigational therapy within 28 days prior to the start of Cycle
- •Vaccination with live vaccines within 28 days prior to the start of Cycle
- •Prior therapy for DLBCL and High-Grade B-cell Lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids.
- •Recent major surgery (within 6 weeks prior to the start of Day 1 of Cycle 1), other than for diagnosis.
- •History of other cancers within 2 years prior to screening.
- •Any active infection that, in the opinion of the investigator, would impact participant safety within 7 days prior to Day 1 of Cycle
- •Serious infection requiring oral or IV antibiotics within 4 weeks prior to Day 1 of Cycle
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
- •Positive test for Hepatitis B/C Viruses (HBV/HCV) and Human T-cell Leukemia Virus (HTLV)-
- •Known infection with HIV.
- •History of progressive multifocal leukoencephalopathy.
- •Suspected active or latent tuberculosis.
- •Clinically significant history of liver disease, including viral or other hepatitis or cirrhosis.
- •Substance abuse, including non-prescription drug and alcohol dependence, within 12 months prior to screening.
- •Pregnant or breastfeeding, or intending to become pregnant during the study within 6 months after the final dose of venetoclax, 9 months after the final dose of polatuzumab vedotin, or 12 months after the final dose of rituximab.
- •History or presence of an abnormal ECG that is clinically significant in the investigator's opinion.
- •Malabsorption syndrome or other condition that would interfere with enteral absorption.
- •Blood transfusion within 14 days prior to screening.
研究组 & 干预措施
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Venetoclax (Drug)
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Polatuzumab Vedotin (Drug)
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Rituximab (Drug)
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Cyclophosphamide (Drug)
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Doxorubicin (Drug)
Venetoclax (Schedule A)
Participants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below:
Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows:
Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
干预措施: Prednisone (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Venetoclax (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Polatuzumab Vedotin (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Rituximab (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Cyclophosphamide (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Doxorubicin (Drug)
Venetoclax (Schedule B)
Participants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below:
Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows:
Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)
次要结局
- Percentage of Participants with Adverse Events (AEs)(Up to 4 years)
- Complete Response (CR) rate at the end of treatment(Up to 4 years)
- Objective Response Rate (ORR) at the end of treatment(Up to 4 years)
- Duration of Response (DOR)(Up to 4 years)
- Progression-Free Survival (PFS)(Up to 4 years)
- Plasma Concentrations of Venetoclax at specified timepoints(Up to 4 years)
- Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints(Up to 4 years)