A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of Venetoclax in Japanese Subjects With Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 14
- 主要终点
- Time to maximum plasma concentration (Tmax) of venetoclax
研究概览
简要总结
This study is evaluating the safety, pharmacokinetic profile and efficacy of venetoclax under a once daily dosing schedule in Japanese participants with hematological malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically documented diagnosis of NHL (and exhausted options considered standard of care) as defined in the World Health Organization classification scheme and relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. Participants with other lymphoproliferative diseases can be considered in consultation with the AbbVie medical monitor
- •Relapsed or refractory multiple myeloma participants must have been previously treated with at least one prior line of therapy and have measurable disease
- •Chronic lymphocytic leukemia/small lymphocytic lymphoma participants must have relapsed or be refractory to standard treatments such as fludarabine based regimens or alkylator based regimens
- •Untreated AML subjects or Relapsed or refractory AML subjects must have been previously treated with at least one prior line of therapy
- •Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1; adequate bone marrow independent of growth factor support per local laboratory reference range; and adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening
- •Participants with a history of autologous or allogenic stem cell transplantation must have adequate blood counts independent of growth factor support and have recovered from any transplant-related toxicity(s) and be at least 100 days post-autologous transplant (multiple myeloma) or 6 month post-autologous transplant (NHL) prior to first dose of study drug or at least 6 months post-allogenic transplant (multiple myeloma) prior to first dose of study drug and not have active graft-versus-host disease (GVHD), i.e., requiring treatment
排除标准
- •NHL participants who have undergone an allogeneic stem cell transplant or were diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia
- •Participant tested positive for HIV
- •Participant has a cardiovascular disability status of New York Heart Association Class greater or equal to 2
- •Participant has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.
- •Participant received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
研究组 & 干预措施
Arm A (Phase 1)
Step-up doses of venetoclax to the designated cohort dose administered in participants with relapsed or refractory (R/R) Non-Hodgkin lymphoma (NHL) or multiple myeloma (MM)
干预措施: venetoclax (Drug)
Arm B (Phase 1)
Step-up doses of venetoclax to the designated dose administered in participants with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
干预措施: venetoclax (Drug)
Arm C (Phase 1)
Step-up doses of venetoclax to the designated dose with the addition of azacitidine administered in participants with acute myeloid leukemia (AML)
干预措施: azacitadine (Drug)
Arm C (Phase 1)
Step-up doses of venetoclax to the designated dose with the addition of azacitidine administered in participants with acute myeloid leukemia (AML)
干预措施: venetoclax (Drug)
Arm D (Phase 2)
Step-up doses of venetoclax to the designated dose with the addition of rituximab in participants with R/R CLL
干预措施: venetoclax (Drug)
Arm D (Phase 2)
Step-up doses of venetoclax to the designated dose with the addition of rituximab in participants with R/R CLL
干预措施: rituximab / IDEC-C2B8 (Drug)
结局指标
主要结局
Time to maximum plasma concentration (Tmax) of venetoclax
时间窗: Approximately 8 days
Number of participants having treatment-emergent adverse events
时间窗: Approximately 2 years
Collect all adverse events at each visit
Maximum plasma concentration (Cmax) of venetoclax
时间窗: Approximately 8 days
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax
时间窗: Approximately 8 days
Objective Response Rate (Phase 2)
时间窗: Approximately 48 months
The proportion of participants with response (e.g., partial, complete response) using IWCLL (International Workshop on Chronic Lymphocytic Leukemia) criteria for CLL participants will be computed for all participants with active disease at baseline (in the opinion of the investigator).
次要结局
- Objective Response Rate (Phase 1)(Approximately 48 months)
- Minimal Residual Disease (MRD)(Approximately 2 years)
- Duration of Response(Approximately 48 months)
- Time to disease progression(Approximately 48 months)
- complete response or remission (CR) rate(Approximately 48 months)
- Partial response or remission (PR) rate(Approximately 48 months)
- Progression Free Survival (PFS)(Approximately 48 months)