A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Relapsed or Refractory Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Treatment-related mortality
研究概览
简要总结
The purpose of this study is to determine the ability of G-CSF to disrupt the bone marrow microenvironment as a means to increase the efficacy of chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).
详细描述
In this study, we will combine G-CSF as priming prior to and during the administration of salvage chemotherapy regimen in ALL. Abundant data suggests that leukemic cells receive key growth and survival signals from the bone marrow microenvironment. Our preclinical data show that 4-5 days of G-CSF treatment is associated with a loss of osteoblasts and decreases expression of key chemokine/ cytokines which support lymphocyte development. The investigators hypothesize that G-CSF will disrupt the protective effects of the bone marrow microenvironment and augment the effect of chemotherapy in adults with ALL. This is a pilot study of G-CSF priming in adult patients with relapsed or refractory ALL to determine the feasibility and to characterize the effect of G-CSF treatment on the marrow microenvironment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Acute lymphoblastic leukemia diagnosed according to WHO criteria (>25% lymphoblasts in BM) which is relapsed or refractory to therapy. Patients with t(9;22) must be refractory to BCR-ABL tyrosine kinase inhibitors.
- •Age ≥ 18 years
- •ECOG performance status ≤
- •Adequate organ function defined as:
- •Calculated creatinine clearance ≥ 50 ml/min
- •AST, ALT, total bilirubin ≤ 2 x institutional ULN except when in the opinion of treating physician elevated levels are due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia)
- •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
- •Previous salvage chemotherapy with ifosfamide and etoposide
- •Pregnant or nursing
- •Received any other investigational agent or cytotoxic chemotherapy 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
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days
Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6
Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6
Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10
Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.
干预措施: G-CSF (Drug)
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days
Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6
Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6
Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10
Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.
干预措施: Ifosfamide (Drug)
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days
Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6
Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6
Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10
Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.
干预措施: Etoposide (Drug)
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days
Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6
Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6
Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10
Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.
干预措施: Dexamethasone (Drug)
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days
Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6
Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6
Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10
Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.
干预措施: Mesna (Drug)
结局指标
主要结局
Treatment-related mortality
时间窗: 30 days after start of treatment
Delayed hematologic recovery
时间窗: Day 46 of treatment
Defined as neutrophil recovery (ANC \> 1,000/mm3) \> 42 days after the start of chemotherapy in the absence of persistent leukemia
次要结局
- Remission duration(2 years)
- Interaction of pretreatment disease and patient characteristics on clinical outcomes(Baseline)
- Complete remission rate cytogenetic complete remission(42 days)
- Overall survival(2 years)
- Disease-free survival(2 years)
- Frequency and severity of adverse events(30 days post treatment)