Conditions: Leukemia, Myeloid, Acute
Keywords: Plerixafor CXCR4 Chemosensitization
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 52
Healthy volunteers: no

Brief summary:
This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML.

We hypothesize that disrupting the interaction between AML blasts and the marrow microenvironment with AMD3100 may enhance the cytotoxic effect of chemotherapy.

Detailed description:
The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although a number of receptor / ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being developed clinically as a mobilization agent for hematopoietic stem cell transplantation. Preclinical data from our group has demonstrated that in murine models, plerixafor can disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II study in patients with relapsed or refractory AML in which plerixafor is administered prior to salvage chemotherapy.

Arms:
arm 1: * AMD3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5

Dose Level 1 AMD3100 dose = 80 mcg/kg/d

Dose Level 2 AMD3100 dose = 160 mcg/kg/d arm 2: * AMD 3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5

Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose)

Interventions: intervention 1: AMD3100 intervention 2: Mitoxantrone intervention 3: Etoposide intervention 4: Cytarabine
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol document: