A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Bcl-2 Inhibitor BGB-11417 in Adult Patients With Mature B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 64
- 试验地点
- 20
- 主要终点
- MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of BGB-11417 monotherapy, define the maximum tolerated dose (MTD) or maximum administered dose and the recommended Phase 2 dose (RP2D) of BGB-11417 monotherapy for the selected B-cell malignancy dose finding cohorts, and evaluate the safety and tolerability of the ramp-up dosing schedule in the evaluated disease types.
详细描述
This study will have 3 cohorts for determining a monotherapy MTD and ramp-up schedule: Cohort A, participants with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R NHL); Cohort B, participants with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with low tumor burden; Cohort C, participants with R/R CLL/SLL with high tumor burden.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of only one of the following:
- •a. Marginal Zone Lymphoma
- •i. R/R extranodal, splenic or nodal disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for MZL is available per investigator's assessment.
- •ii. Active disease requiring treatment.
- •b. Follicular Lymphoma
- •i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that has relapsed after, or been refractory to, ≥ 1 line of anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for FL is available per investigator's assessment.
- •ii. Active disease requiring treatment.
- •c. Diffuse Large B-cell Lymphoma
- •i. R/R DLBCL defined as disease that relapsed after, or been refractory to, at least one line of anti-CD20 antibody based chemoimmunotherapy for ≥ 2 consecutive cycles, and no effective standard therapy for DLBCL is available per investigator's assessment.
- •ii. Active disease requiring treatment.
- •d. Transformed indolent B-cell NHL
- •i. Any lymphoma otherwise eligible for Cohort A that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Cohort A.
- •ii. Active disease requiring treatment.
- •Cohorts B and C
- •a. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria:
- •i. R/R disease defined as disease that has relapsed after, or been refractory to, ≥ 1 line of standard therapy for ≥ 2 consecutive cycles, and no effective standard therapy is available per investigator's assessment.
- •ii. Requiring treatment based on IWCLL criteria.
- •Measurable disease by computed tomography/magnetic resonance imaging, defined as:
- •CLL: At least 1 lymph node > 1.5 centimeters (cm) in longest diameter and measurable in 2 perpendicular dimensions. For Cohort B, participants should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.
- •DLBCL, FL, MZL, SLL: At least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions. For MZL isolated splenomegaly is considered to indicate measurable disease for this study. For SLL, participants in Cohort B should not meet with the definition of high tumor burden, which is required for participants enrolled in Cohort C.
排除标准
- •Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
- •Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.
- •Known central nervous system involvement by lymphoma/leukemia.
- •Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome.
- •Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric cell therapy unless ≥ 6 months after cell infusion.
- •Prior allogeneic stem cell transplant.
研究组 & 干预措施
Cohort B: R/R CLL/SLL (low tumor burden)
Participants with low tumor burden R/R CLL/SLL will receive oral BGB-11417 until the MTD (or MAD) and the RP2D can be determined.
干预措施: BGB-11417 (Drug)
Cohort C: R/R CLL/SLL (high tumor burden)
Participants in this cohort will not be enrolled until the RP2D for Cohort B is established. Participants will be treated with the monotherapy ramp-up schedule and the RP2D established in Cohort B.
干预措施: BGB-11417 (Drug)
Cohort A: R/R NHL
Participants with R/R NHL, including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), or transformed NHL, will receive oral BGB-11417 until the MTD (or maximum ascending dose [MAD]) and the RP2D can be determined.
干预措施: BGB-11417 (Drug)
结局指标
主要结局
MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
时间窗: Approximately 3 years
RP2D Of BGB-11417
时间窗: Approximately 3 years
The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data.
Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs)
时间窗: Approximately 3 years
All AEs, including DLT events, will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (or the Grading Scale for Hematologic Toxicity in CLL Studies as appropriate).
Incidence And Severity Of Tumor Lysis Syndrome-relevant Events
时间窗: Approximately 3 years
MTD Of BGB-11417 As Recommended By The Bayesian Logistic Regression Model Or The MAD
时间窗: Approximately 3 years
RP2D Of BGB-11417
时间窗: Approximately 3 years
The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data.
Incidence And Severity Of Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events (AEs) Leading To Discontinuation, And Dose-Limiting Toxicities (DLTs)
时间窗: Approximately 3 years
All AEs, including DLT events, will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (or the Grading Scale for Hematologic Toxicity in CLL Studies as appropriate).
Incidence And Severity Of Tumor Lysis Syndrome-relevant Events
时间窗: Approximately 3 years
次要结局
- PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417(Up to 24 hours postdose)
- Overall Response Rate (ORR) Of BGB-11417 Monotherapy(Approximately 3 years)
- Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Last Measurable Concentration At Steady State (AUClast,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Trough Concentration At Steady State (Ctrough,ss) Of BGB-11417(Up to 24 hours postdose)
- Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration (tmax) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Terminal Half-life (t1/2) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Apparent Volume Of Distribution (Vz/F) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To Last Measurable Concentration At Steady State (AUClast,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of BGB-11417(Up to 24 hours postdose)
- PK As Assessed By Time To Maximum Observed Plasma Concentration At Steady State (tmax,ss) Of BGB-11417(Up to 24 hours postdose)
- Overall Response Rate (ORR) Of BGB-11417 Monotherapy(Approximately 3 years)