A Safety and Tolerability Trial of Crenolanib and Chemotherapy With Cytarabine and Anthracyclines in Patients With Newly Diagnosed Acute Myeloid Leukemia With FLT3 Activating Mutations
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 9
- 主要终点
- Clinical Response to Crenolanib With Standard Induction Chemotherapy
研究概览
简要总结
This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unequivocal diagnosis of AML based on the WHO classification, excluding acute promyelocytic leukemia
- •No prior therapy for AML, except for hydroxyurea, in this setting is allowed.
- •Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents
- •Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations
- •Age ≥18 years
- •ECOG PS 0 - 2
- •Adequate liver function, defined as normal total bilirubin, ALT ≤2.0x ULN, and AST ≤2.0x ULN measured within 24 hours prior to crenolanib commencement
- •Adequate renal function, defined as serum creatinine ≤1.5x ULN or GFR >50 mL/min
- •Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP)
- •Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation
- •WOCBP must practice contraception. Acceptable methods of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, tubal ligations, and abstention
- •Male patients (except those with prior surgical contraceptive procedures) with female partners who are of childbearing potential: Recommendation is for male and partner to use effective contraceptive methods, such as latex condoms, during the study
- •Able and willing to provide written informed consent
排除标准
- •Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
- •Active CNS leukemia
- •Subject with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
- •NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
- •Unable to swallow pills
- •Major surgical procedures within 14 days of administration of crenolanib (does not include line placement as needed for chemotherapy administration).
- •Unwillingness or inability to comply with protocol.
- •Concurrent use of other investigational agents.
- •Subjects who are not eligible for standard chemotherapy
研究组 & 干预措施
Cohort A
Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: crenolanib (Drug)
Cohort A
Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: cytarabine (Drug)
Cohort A
Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: daunorubicin (Drug)
Cohort B
Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: crenolanib (Drug)
Cohort B
Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: cytarabine (Drug)
Cohort B
Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID.
干预措施: idarubicin (Drug)
结局指标
主要结局
Clinical Response to Crenolanib With Standard Induction Chemotherapy
时间窗: 2 years
To determine the response rate to crenolanib. Complete remission (CR) response criteria includes a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, the absence of Auer rods and extramedullary leukemia, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. Complete remission with incomplete blood count recovery (CRi) response includes all CR criteria met, except participant do not achieve either platelet or ANC recovery. Composite Complete CR response includes all subjects who achieve a CR and CRi. Partial Response (PR) response includes all CR criteria met except a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but within 5-25% or bone marrow blasts \<5% with persistent Auer rods. Refractory Disease response includes subjects who do not satisfy the criteria for CR, CRi or PR.
次要结局
- 3-Year Overall Survival(3 years)