Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Response Rate of Crenolanib Besylate Combination Therapy
研究概览
简要总结
This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine
详细描述
For each arm:
The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.
Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.
Enrollment to be simultaneous to each arm.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
- •Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
- •Arm 2: Subjects must have received at least one prior therapy and a maximum of three prior therapies. No prior treatment with 5-Azacitidine is allowed in this arm.
- •FLT3 mutation positive (ITD, TKD or other)
- •ECOG PS 0-2
- •Adequate liver and renal function
- •Negative pregnancy test
- •Extramedullary leukemia allowed except CNS disease
排除标准
- •Arm 1 and 2 Exclusion:
- •<5% blasts in marrow or blood at time of screening
- •Active HIV, hepatitis B or C
- •CNS leukemia
- •Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
- •Patient with AML-M3 (APL)
- •Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
研究组 & 干预措施
Arm 2 crenolanib besylate combination
Arm 2 patients will receive crenolanib besylate and azacytidine.
干预措施: Azacytidine (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Crenolanib besylate (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Idarubicin (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Cytarabine (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Mitoxantrone (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Etoposide (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: Fludarabine (Drug)
Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
干预措施: G-CSF (Drug)
Arm 2 crenolanib besylate combination
Arm 2 patients will receive crenolanib besylate and azacytidine.
干预措施: Crenolanib besylate (Drug)
结局指标
主要结局
Response Rate of Crenolanib Besylate Combination Therapy
时间窗: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.
To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include 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. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.
次要结局
未报告次要终点