Clinical trial NCT00906945
Conditions: Leukemia, Myeloid, Acute
Keywords: stem cell mobilization chemosensitization CXCR4 SDF-1 CXCL-12
Sponsor: Washington University School of Medicine
Start date: 2011-02-01; Completion date: 2015-09-01
Enrollment: 39 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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

Detailed description:
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.

Arms: arm 1: * 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 arm 2: * 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 arm 3: * 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 arm 4: * 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 arm 5: * 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 arm 6: * 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
Interventions: intervention 1: G-CSF intervention 2: Plerixafor intervention 3: Mitoxantrone intervention 4: Etoposide intervention 5: Cytarabine
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol documents: