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临床试验/NCT00906945
NCT00906945已完成1 期

Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia

Washington University School of Medicine3 个研究点 分布在 1 个国家目标入组 39 人开始时间: 2011年2月最近更新:
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适应症
干预措施

试验速览

阶段
1 期
状态
已完成
入组人数
39
试验地点
3
主要终点
Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.

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 this study, we seek to maximize blockage of the SDF-1/CXCR4 axis through the following:

  1. Addition of G-CSF, which down regulates SDF-1 expression and acts synergistically with plerixafor in stem cell mobilization
  2. Intravenous instead of subcutaneous dosing of plerixafor to improve kinetics of administration.
  3. Dose escalation of plerixafor and twice daily dosing to maintain maximum CXCR4 blockade.

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 70 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Acute myeloid leukemia diagnosed by WHO criteria with one of the following:
  • •Primary refractory disease following no more than 2 cycles of induction chemotherapy
  • •First relapse with no prior unsuccessful salvage chemotherapy
  • •Age between 18 and 70 years old
  • •ECOG performance status ≤ 3
  • •Adequate organ function defined as:
  • •Calculated creatinine clearance ≥ 50 ml/min
  • •AST, ALT, total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia)
  • •Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
  • •Are surgically or biologically sterile or willing to practice acceptable birth control, as follows:
  • •Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence.
  • •Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period
  • •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 ≥ 20 x 103 /mm3
  • •Active CNS involvement with leukemia
  • •Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
  • •Pregnant or nursing
  • •Received any other investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within the preceding 2 weeks
  • •Received colony stimulating factors filgrastim or sargramostim within 1 week or pegfilgrastim within 2 weeks of study
  • •Severe concurrent illness that would limit compliance with study requirements

研究组 & 干预措施

Dose Level 1

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

Dose Level 1

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

Dose Level 1

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

Dose Level 1

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

Dose Level 1

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

Dose Level 2

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

Dose Level 2

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

Dose Level 2

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

Dose Level 2

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

Dose Level 2

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

Dose Level 3

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

Dose Level 3

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

Dose Level 3

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

Dose Level 3

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

Dose Level 3

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

Dose Level 4

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

Dose Level 4

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

Dose Level 4

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

Dose Level 4

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

Dose Level 4

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

Dose Level 5

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

Dose Level 5

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

Dose Level 5

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

Dose Level 5

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

Dose Level 5

Experimental
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

MTD - Phase II

Experimental
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: G-CSF (Drug)

MTD - Phase II

Experimental
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Plerixafor (Drug)

MTD - Phase II

Experimental
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Mitoxantrone (Drug)

MTD - Phase II

Experimental
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Etoposide (Drug)

MTD - Phase II

Experimental
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

干预措施: Cytarabine (Drug)

结局指标

主要结局

Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC

时间窗: Completion of Phase I enrollment (17 months)

Phase II: Complete Response Rate (CR+CRi)

时间窗: 45 days

* Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1,000/mm3, platelet count \> 100,000/mm3. * Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia \<1,000/mm3 or thrombocytopenia \<100,000/mm3.

次要结局

  • Time to Hematologic Recovery as Measured by Time to Platelet Recovery(Up to 62 days after treatment)
  • Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells(6 hours after plerixafor)
  • Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity(6 hours after plerixafor)
  • Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity(6 hours after plerixafor)
  • Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency(30 days following end of treatment)
  • Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery(Up to 62 days after treatment)
  • Time to Progression(2 years)
  • Time to Treatment Failure(8 days)
  • Overall Survival(Median follow-up was 34.6 months)
  • Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count(6 hours after plerixafor)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (3)

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