A Phase 3b, Single-Arm, Multicenter Open-Label Study of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in AML Patients Ineligible for Intensive Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 16
- 主要终点
- Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
研究概览
简要总结
A study evaluating the effectiveness and safety of venetoclax, in combination with azacitidine or decitabine, in an outpatient setting for treatment-naïve participants with AML who are ineligible for intensive chemotherapy.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria
- •Participant is deemed by the investigator to be an appropriate candidate for outpatient ramp-up of venetoclax
- •Participant is not eligible to receive treatment with standard cytarabine and anthracycline induction regimens
- •Participant has not received prior treatment for AML (treatment naïve) with the exception of hydroxyurea
- •Participant has no evidence of spontaneous tumor lysis syndrome (TLS) at Screening
- •Participant can have progressed from myelodysplastic syndrome (MDS) or be considered to have secondary AML and could have been treated with growth factors or other agents with the exception of hypomethylating agents
- •Participant has adequate kidney, liver, and hematology laboratory values as detailed in the protocol
- •Has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 3
排除标准
- •Has a history of the following conditions:
- •Acute promyelocytic leukemia
- •Known active central nervous system involvement with AML
- •Positive for HIV (HIV testing is not required)
- •Positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months
- •Cardiovascular disability status of New York Heart Association Class > 2
- •Chronic respiratory disease that requires continuous oxygen or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study
- •Malabsorption syndrome or other condition that precludes enteral route of administration
- •Has a history of other malignancies within 2 years 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
研究组 & 干预措施
Venetoclax 400 mg + azacitidine 75 mg
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Azacitidine (75 mg/m^2) was administered subcutaneously or intravenously per investigator's choice and institutional practice for 7 days beginning on Day 1 of each 28-day cycle.
干预措施: Venetoclax (Drug)
Venetoclax 400 mg + azacitidine 75 mg
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Azacitidine (75 mg/m^2) was administered subcutaneously or intravenously per investigator's choice and institutional practice for 7 days beginning on Day 1 of each 28-day cycle.
干预措施: Azacitidine (Drug)
Venetoclax 400 mg + decitabine 20 mg
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Decitabine (20 mg/m^2) was administered intravenously per investigator's choice and institutional practice for 5 days beginning on Day 1 of each cycle.
干预措施: Venetoclax (Drug)
Venetoclax 400 mg + decitabine 20 mg
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Decitabine (20 mg/m^2) was administered intravenously per investigator's choice and institutional practice for 5 days beginning on Day 1 of each cycle.
干预措施: Decitabine (Drug)
结局指标
主要结局
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
时间窗: Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.
The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML: CR: Absolute neutrophil count (ANC) \> 10\^3/μL (1,000/μL), platelets \> 10\^5/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with \< 5% blasts CRi: Bone marrow with \< 5% blasts, and absolute neutrophils of ≤ 10\^3/μL or platelets ≤ 10\^5/μL
次要结局
- Percentage of Participants With Complete Remission (CR)(Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.)
- Percentage of Participants With Post-baseline Transfusion Independence(From the first dose of study drug to the last dose of study drug +30 days, or death, or initiation of post-treatment therapy, whichever occurred earliest. Median time on follow-up was 183.5 days and 195.0 days, respectively.)
- Percentage of Participants With Complete Remission With Incomplete Blood Count Recovery (CRi)(Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.)