A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 222
- 试验地点
- 10
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of ABT-199 under a once daily dosing schedule. Two arms will be implemented for dose escalation: Arm A, CLL/SLL subjects and Arm B, NHL subjects. Arm A is designed to enroll approximately 116 subjects with relapsed or refractory CLL or SLL and Arm B is designed to enroll approximately 95 subjects with relapsed or refractory NHL. Fifty-six subjects were enrolled in Arm A and approximately 55 subjects will be enrolled in Arm B during the dose escalation portion of the study, with the objective of defining dose limiting toxicities (DLTs) and the MTD. Once the MTD is declared for the arm, approximately 60 additional CLL/SLL subjects in Arm A and approximately 20 additional DLBCL subjects and 20 additional follicular lymphoma subjects in Arm B will be enrolled in an expanded safety portion of the study at the recommended phase 2 dose (RPTD) and schedule.
详细描述
Interventional Study Design - Primary Purpose: Determination of safety and tolerability.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must have either:
- •(Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of the Investigator. Subject must have relapsed following or be refractory to standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or alkylator (chlorambucil, bendamustine) based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care, or
- •(Arm B) relapsed or refractory NHL and require treatment in the opinion of the Investigator. Subject must have histologically documented diagnosis of NHL as defined in the World Health Organization classification scheme, except as noted in the exclusion criteria. Subject must have relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care. Subjects with other lymphoproliferative diseases can be considered in consultation with the Abbott medical monitor.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to
- •Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
- •Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
排除标准
- •CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant or has been diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
- •Subject has tested positive for HIV.
- •Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to
- •Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
- •Subject 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.
- •Subject has 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 (CLL/SLL subjects)
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects
干预措施: ABT-199 (Drug)
Arm B (NHL subjects)
Non-Hodgkin lymphoma (NHL) subjects
干预措施: ABT-199 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months)
Determination of plasma peak concentration (Cmax) of ABT-199
时间窗: Up to Week 24 for ABT-199
Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Determination of trough concentration (Ctrough) of ABT-199
时间窗: Up to Week 24 for ABT-199
Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RPTD), and lead-in period regimen
时间窗: Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing)
Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Determination of area under the concentration versus time curve (AUC) of ABT-199
时间窗: Up to Week 24 for ABT-199
Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
次要结局
- Preliminary efficacy assessment(Starting Week 4 for clinical disease progression and Week 6 for tumor response; and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months))
- Minimal residual disease collection (MRD)(At least 2 months after the CR, CRi criteria for tumor response are first met. Every 12 weeks thereafter, until MRD negativity has been achieved (in peripheral blood).)
- Food Effect - Cmax(Approximately 3 days)
- Food Effect - Tmax(Approximately 3 days)
- Food Effect - AUC(Approximately 3 days)