A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 212
- 试验地点
- 23
- 主要终点
- Time to Cmax (peak time, Tmax),
研究概览
简要总结
This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of venetoclax (ABT-199) in combination with posaconazole.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
- •Subject must have received no prior treatment for AML with the exception of hydroxyurea
- •Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
- •Subject must have adequate kidney and liver function as described in the protocol
排除标准
- •Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
- •Subject has history of Myeloproliferative Neoplasm (MPN).
- •Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
- •Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
- •Subject has acute promyelocytic leukemia.
- •Subject has known active central nervous system involvement with AML.
- •Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.
- •Subject has a history of other malignancies prior to study entry, with the exception of:
- •Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
- •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.
- •Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.
研究组 & 干预措施
ABT-199 + Azacitidine
Treatment Naive Acute Myelogenous Leukemia
干预措施: ABT-199 (Drug)
ABT-199 + Azacitidine
Treatment Naive Acute Myelogenous Leukemia
干预措施: Azacitidine (Drug)
ABT-199 + Decitabine
Treatment Naive Acute Myelogenous Leukemia
干预措施: ABT-199 (Drug)
ABT-199 + Decitabine
Treatment Naive Acute Myelogenous Leukemia
干预措施: Decitabine (Drug)
ABT-199+Decitabine+Posaconazole
Treatment Naive Acute Myelogenous Leukemia
干预措施: Posaconazole (Drug)
ABT-199+Decitabine+Posaconazole
Treatment Naive Acute Myelogenous Leukemia
干预措施: ABT-199 (Drug)
ABT-199+Decitabine+Posaconazole
Treatment Naive Acute Myelogenous Leukemia
干预措施: Decitabine (Drug)
结局指标
主要结局
Time to Cmax (peak time, Tmax),
时间窗: For approximately 5 days following a single dose of ABT-199.
The time at which maximum plasma concentration (Cmax) is observed.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Measured up to 1 year after the last subject last dose
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug.
Maximum observed plasma concentration (Cmax)
时间窗: For approximately 5 days following a single dose of ABT-199.
Maximum observed concentration, occurring at Tmax.
The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
时间窗: For approximately 5 days following a single dose of ABT-199.
The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
Half-Life (t1/2)
时间窗: For approximately 5 days following a single dose of ABT-199.
The time required for the concentration of the drug to reach half of its original value.
Clearance (CL)
时间窗: For approximately 5 days following a single dose of ABT-199.
Clearance is defined as the rate at which drug is cleared from the blood.
Complete Remission Rate
时间窗: Measured up to 1 year after the last subject last dose
Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
Complete Remission with incomplete blood count recovery rate
时间窗: Measured up to 1 year after the last subject last dose
Complete Remission with incomplete blood count recovery rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.
Overall Response Rate
时间窗: Measured up to 1 year after the last subject last dose
Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission (PR) per the International Working Group criteria for AML.
Overall Survival
时间窗: Measured up to 1 year after the last subject last dose
Overall survival will be defined as the number of days from the date of first dose to the date of death.
次要结局
- Event Free Survival(Measured up to 1 year after the last subject last dose)
- Duration of Response(Measured up to 1 year after the last subject last dose)