A Phase 1b Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Relapsed or Refractory Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Their Standard Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 9
- 主要终点
- Determine recommended phase two dose (RPTD) of ABT-199
研究概览
简要总结
The primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and the recommended phase two dose (RPTD) of ABT-199 when administered in subjects with relapsed /refactory multiple myeloma who are receiving bortezomib and dexamethasone as their standard therapy.
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
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1
- •Diagnosis of multiple myeloma previously treated with at least 1 prior line of therapy (dose escalation only) or (safety expansion only) received treatment with a proteasome inhibitor or an IMiD(r) or immunomodulatory agent (e.g., thalidomide, lenalidomide). Induction therapy and following stem cell transplant are considered a single line of therapy.
- •Measurable disease at Screening: Serum monoclonal protein greater than or equal to 1 g/dL by protein electrophoresis, or greater than or equal to 200 mg monoclonal protein in the urine on 24-hr electrophoresis, or serum immunoglobulin free light chain greater than or equal to 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio.
- •Subjects with a history of autologous or allogenic stem cell transplant must have adequate bone marrow independent of any growth factor support, and have recovered from any transplant related toxicity(s); and either greater than 100 days post-autologous transplant (prior to first dose of study drug) or greater than or equal to 6 months post-allogenic transplant (prior to first dose of study drug) and not have active graft-versus-host disease (i.e., requiring treatment).
- •Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
排除标准
- •Exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
- •Cardiovascular disability status of New York Heart Association Class greater than 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.
- •Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, pulmonary or hepatic disease, that in the opinion of the investigator, would adversely affect his/her participation in the study.
- •History of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions: adequately treated in situ carcinoma of the cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- •Tested positive for HIV or hepatitis.
研究组 & 干预措施
ABT-199 + BTZ/Dex Dose Escalation Cohorts
Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.
干预措施: ABT-199 (Drug)
ABT-199 + BTZ/Dex Dose Escalation Cohorts
Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.
干预措施: bortezomib (Drug)
ABT-199 + BTZ/Dex Dose Escalation Cohorts
Evaluate the safety and pharmacokinetics profile of ABT-199 administered with standard therapy bortezomib and dexamethasone in a dose escalation scheme in approximately 54 subjects.
干预措施: dexamethasone (Drug)
ABT-199 + BTZ/Dex Safety Expansion Cohort
Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
干预措施: ABT-199 (Drug)
ABT-199 + BTZ/Dex Safety Expansion Cohort
Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
干预措施: bortezomib (Drug)
ABT-199 + BTZ/Dex Safety Expansion Cohort
Safety expansion cohort to further evaluate recommended phase two dose (RPTD) of ABT-199 administered with standard therapy bortezomib and dexamethasone in approximately 12 subjects.
干预措施: dexamethasone (Drug)
结局指标
主要结局
Determine recommended phase two dose (RPTD) of ABT-199
时间窗: Minimum first cycle of dosing (21 days
ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.
Determination of peak concentration (Cmax) of ABT-199
时间窗: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
Determine maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of ABT-199
时间窗: Minimum first cycle of dosing (21 days)
ABT-199 will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicities information from all subjects.
Determination of trough concentration (Ctrough) of ABT-199
时间窗: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
Determination of area under the concentration versus time curve (AUC) of ABT-199
时间窗: Approximately 5 days in Cycle 1 then on Day 1 of Cycles 2,4,6,8
Blood samples for pharmacokinetic analysis of ABT-199 will be collected at designated timepoints
Number of participants with adverse events
时间窗: From subject's first dose of ABT-199 until 30 days after subject's last dose of ABT-199; up to 2 years following last subject first dose.
Collect all adverse events at each visit.
次要结局
- Time to Disease Progression(Measured up to 48 months after the last subject has enrolled in the study)
- Duration of Response(Measured up to 48 months after the last subject has enrolled in the study)
- Objective Response Rate(Measured up to 48 months after the last subject has enrolled in the study)