A Phase 2 Study of ABT-199 in Subjects With Acute Myelogenous Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 主要终点
- Objective Remission Rate
研究概览
简要总结
This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML).
详细描述
The primary objective was to evaluate the preliminary efficacy of venetoclax administered orally in participants with relapsed and/or refractory (R/R) acute myelogenous leukemia (AML) or frontline therapy in patients with AML who were unfit for intensive therapy. The secondary objective was to evaluate the preliminary safety of venetoclax administered orally in patients with AML. The first portion of the study was to consist of 19 participants with the objective of evaluating anti-tumor effects and confirming the safety of the regimen. The second portion (expansion) was to consist of 35 additional subjects to evaluate anti-tumor effects and safety and was to commence if an adequate efficacy signal (i.e., ≥ 5/19 achieved complete remission [CR], CR with incomplete bone marrow recovery [CRi] or partial remission [PR]) had been observed in the first portion of the study. The criterion for success would have been met if ≥ 16 of 54 participants achieved remission. The efficacy signal from first portion of the study was deemed insufficient for enrollment into the second portion of the study, as 4 of the 19 subjects achieved CR/CRi. During the trial, a number of participants were in screening at the point of the interim analysis. Given the early signs of clinical activity of venetoclax, disease severity, and prognosis of these participants without available options for therapy, they were allowed to initiate treatment ahead of completion of the interim analysis. Therefore, 32 participants were enrolled. No additional participants were screened or treated after the interim analysis was completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histological or cytological confirmation of relapsed or refractory acute myelogenous leukemia (AML) (by World Health Organization [WHO] classification) or untreated AML in participants who are unfit for intensive therapy.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to
- •Participant must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula using ideal body mass (IBM) instead of mass.
- •Participant must have adequate liver function as demonstrated by:
- •aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN)*
- •alanine aminotransferase (ALT) ≤ 3.0 × ULN*
- •bilirubin ≤ 1.5 × ULN* *unless considered due to leukemic organ involvement. (Participants with Gilbert's Syndrome may have had a bilirubin > 1.5 × ULN per discussion between the investigator and AbbVie medical monitor)
排除标准
- •Participant has received acute anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of ABT-
- •Participant has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
- •Participant has received potent Cytochrome P450, family 3, subfamily A (CYP3A) inducers (such as rifampin, carbamazepine, phenytoin and St. John's wort) and warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect) within 7 days prior to the first dose of study drug.
- •Participant has received CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 5 days prior to the first dose of study drug.
- •Participant has a white blood cell count > 25 x 10^9/L.
- •Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).
- •Participants with known active central nervous system (CNS) disease.
研究组 & 干预措施
ABT-199
Continuous dosing of venetoclax (ABT-199) QD (once daily) beginning with dose-escalation on Week 1 Day 1. Participants received a dose of 20 mg of ABT-199 on Week 1 Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, 400 mg on Day 5, 800 mg on Day 6 and QD thereafter.
干预措施: ABT-199 (Drug)
结局指标
主要结局
Objective Remission Rate
时间窗: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
The objective remission rate (ORR) was defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR) per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL. Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.
次要结局
- Rate of Minimal Residual Disease (MRD) Negativity(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Complete Remission With Incomplete Marrow Recovery (CRi) Rate(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Complete Remission Rate and Complete Remission With Incomplete Marrow Recovery (CRi) Rate(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Percentage of Participants Who Received Subsequent Stem Cell Transplant(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Complete Remission Rate(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Duration of Remission(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Progression-free Survival(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)
- Overall Survival(Measured up to 2 years after the last subject had enrolled in the study.)
- Time to Progression(When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier)