A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status
Phase I Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AC220 When Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
-
T'Bilisi、乔治亚州
- Chemotherapy and Immunotherapy Clinic
-
T'bilisi、乔治亚州
- Hematology and Chemotherapy Clinic
-
-
-
-
Alabama
-
Birmingham、Alabama、美国、35294
- University of Alabama at Birmingham
-
-
Nebraska
-
Omaha、Nebraska、美国、68198
- University Of Nebraska Medical Center
-
-
Texas
-
Houston、Texas、美国、77030
- MD Anderson Cancer Center
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Males and females age ≥ 18 years;
Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:
- Refractory to at least 1 cycle of induction chemotherapy, or
- Relapsed after at least 1 cycle of induction chemotherapy, or
- Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
- Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
- In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;
- Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
- Serum creatinine ≤ 2.0 mg/dL;
- Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
- Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
- Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
- Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
- Written informed consent must be provided.
Exclusion Criteria:
- Histologic diagnosis of acute promyelocytic leukemia;
- Clinically active central nervous system leukemia;
- Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);
- Bone marrow transplant within 2 months prior to study;
- Active, uncontrolled infection;
- Major surgery within 4 weeks prior to study;
- Radiation therapy within 4 weeks prior to, or concurrent with, study;
- Human immunodeficiency virus positivity;
- Active hepatitis B or C or other active liver disease;
- Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
- Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:AC220
Determine safety, tolerability and pharmacokinetic (PK) parameters of AC220
|
Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials.
Requires reconstitution by a pharmacist, and must be stored securely and protected from light.
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 30 days post last dose
|
Baseline up to 30 days post last dose
|
Number of Participants With Treatment-emergent Treatment-related Grade 3 or 4 Adverse Events By At Least 10% of All Participants By Dose Group Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 30 days post last dose
|
Baseline up to 30 days post last dose
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 28 days after the last dose, up to approximately 3 years
|
Progressive disease response criteria included doubling of blast count % in bone marrow (biopsy or aspirate) from baseline; considering measurements starting on Study Day 15, doubling of blast count % in blood from baseline; death determined to be related to disease or disease progression; and investigator reported disease progression.
|
Baseline up to 28 days after the last dose, up to approximately 3 years
|
Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 28 days after the last dose, up to approximately 3 years
|
Complete Response (CR) response criteria included either a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying BM assessment.
CRp response included all CR criteria met, except participant did not experience a platelet recovery (ANC recovery required).
CRi response included a qualifying BM result, but not an ANC recovery.
Participants may or may not have had a platelet recovery and were not required to be transfusion independent.
Partial remission (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy.
Nonresponders (NR) had a pre- and 1 or more post-baseline BM assessment carried out, but results did not meet any response criteria.
Participants who were not evaluable (NE) did not have at least 14 days of treatment and were not assessed.
|
Baseline up to 28 days after the last dose, up to approximately 3 years
|
Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 28 days after the last dose, up to approximately 3 years
|
Complete Response (CR) response criteria included either a post-baseline bone marrow biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying bone marrow assessment.
CRp response included all CR criteria met except participant did not experience a platelet recovery.
Participants must have experienced an ANC Recovery.
CRi response included a qualifying bone marrow result, but did not experience an ANC recovery.
Participants may or may not have experienced a platelet recovery and were not required to be transfusion independent.
Partial remission (PR) response included a decrease of ≥50% in % blasts in the bone marrow aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy.
Nonresponders (NR) had a pre- and 1 or more post-baseline bone marrow assessment carried out, but results did not meet any of the CR or PR or progressive disease criteria.
|
Baseline up to 28 days after the last dose, up to approximately 3 years
|
Number of Participants With Hematologic Improvement Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
大体时间:Baseline up to 28 days after the last dose, up to approximately 3 years
|
Hematologic improvement is summarized in terms of Erythroid Response (HI-E), Platelet Response (HI-P), Neutrophil Response (HI-N), and Hematologic Improvement (HI). For post-treatment results, HI-E major responders had >2 g/dL increase in hemoglobin for at least 1 result after first treatment and transfusion independent; minor responders 1 to 2 g/dL increase in hemoglobin for at least 1 result post first treatment and a 50% decrease in red blood cell transfusion requirements. For HI-P, major responders had ≥30 × 10^9/L increase in platelet count and transfusion independent; minor responders had 50% or more increase in platelet count with a net increase between 10 to 30 × 10^9/L and 50% decrease in platelet transfusion requirements. For HI-N, major responders had an increase in absolute neutrophil count (ANC) of 100% or an absolute increase of more than 0.5 × 10^9/L (whichever is greater); minor responders had an increase in ANC of 100% but an absolute increase of <0.5 × 10^9/L. |
Baseline up to 28 days after the last dose, up to approximately 3 years
|
合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他研究编号
- CP0001
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
- 企业社会责任
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
急性髓性白血病的临床试验
-
Shenzhen Second People's Hospital招聘中白血病 | 骨髓的 | 慢性的 | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | 积极的中国
AC220的临床试验
-
Daiichi Sankyo, Inc.Ambit Biosciences Corporation完全的
-
Daiichi Sankyo, Inc.完全的
-
Daiichi Sankyo, Inc.完全的反洗钱美国, 大韩民国, 台湾, 英国, 法国, 澳大利亚, 西班牙, 意大利, 加拿大, 新加坡, 德国, 荷兰, 香港, 比利时, 克罗地亚, 捷克语, 匈牙利, 波兰, 塞尔维亚
-
Children's Oncology GroupNational Cancer Institute (NCI)完全的
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)完全的复发性急性髓性白血病 | 具有 FLT3/ITD 突变的急性髓性白血病 | 难治性急性白血病美国