A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.
研究概览
简要总结
In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
详细描述
In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:
- •Primary refractory disease following ≥ 1 round of induction chemotherapy
- •First relapse or higher
- •Age between 18 and 70 years
- •ECOG performance status ≤ 2
- •Adequate organ function defined as:
- •Creatinine ≤ 1.5 x institutional ULN
- •AST ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- •ALT ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- •Total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- •Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
- •Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study
- •Able to provide signed informed consent prior to registration on study
排除标准
- •Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
- •Peripheral blood blast count ≥ 50 x 103 /mm3
- •Active CNS involvement with leukemia
- •Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
- •Pregnant or nursing
- •Concurrently receiving any other investigational agent
- •Received colony stimulating factors filgrastim or sargramostim within 48 hours or pegfilgrastim within 14 days of study
- •Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (excluding hydroxyurea)
- •Severe concurrent illness that would limit compliance with study requirements
研究组 & 干预措施
Dose Level 2
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Etoposide (Drug)
Dose Level 1
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Plerixafor (Drug)
Dose Level 1
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Mitoxantrone (Drug)
Dose Level 1
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Etoposide (Drug)
Dose Level 1
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Cytarabine (Drug)
Dose Level 2
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Plerixafor (Drug)
Dose Level 2
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Mitoxantrone (Drug)
Dose Level 2
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Cytarabine (Drug)
Dose Level 3
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Plerixafor (Drug)
Dose Level 3
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Mitoxantrone (Drug)
Dose Level 3
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Etoposide (Drug)
Dose Level 3
Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5
干预措施: Cytarabine (Drug)
结局指标
主要结局
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.
时间窗: Days 1-42 (all patients have to complete)
次要结局
- To determine the time to hematologic recovery(For up to 2 years)
- To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.(Baseline, 6 hours)
- To determine the time to event-free survival(For up to 2 years)
- To determine the time to relapse-free survival(For up to 2 years)
- To determine the safety and tolerability of plerixafor in combination with MEC(Minimum of 30 days following completion of treatment)
- To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.(Predose, 15 min, 30 min , and 10 hrs)
- To determine the time to duration of remission(For up to 2 years)
- To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.(Between days 15-42)
- To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.(Baseline, 6 hours)
- To determine the time to overall survival(For up to 2 years)