Disrupting the Bone Marrow Microenvironment With G-CSF in Acute Lymphoblastic Leukemia
- Conditions
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Interventions
- Registration Number
- NCT01331590
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
-
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.
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Age ≥ 18 years
-
ECOG performance status ≤ 3.
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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)
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Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study.
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Able to provide signed informed consent prior to registration on study.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna G-CSF 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. G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna Ifosfamide 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. G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna 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. G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna Etoposide 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. G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Treatment-related mortality 30 days after start of treatment Delayed hematologic recovery 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
- Secondary Outcome Measures
Name Time Method Frequency and severity of adverse events 30 days post treatment Remission duration 2 years Every 6 months
Interaction of pretreatment disease and patient characteristics on clinical outcomes Baseline Morphology, cytogenetics, immunophenotype, WBC, and performance status
Complete remission rate cytogenetic complete remission 42 days Overall survival 2 years Every 6 months
Disease-free survival 2 years Every 6 months
Trial Locations
- Locations (2)
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States