Leukemia, Myeloid, Acute
Conditions
Brief summary
In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
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 current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
Interventions
DRUGPlerixafor
DRUGMitoxantrone
DRUGEtoposide
DRUGCytarabine
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Acute myeloid leukemia diagnosed according to WHO criteria with one of the following: * Primary refractory disease following ≥ 1 round of induction chemotherapy * First relapse or higher * Age between 18 and 70 years * ECOG performance status ≤ 2 * Adequate organ function defined as: * Creatinine ≤ 1.5 x institutional ULN * AST ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia) * ALT ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia) * Total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia) * Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram * 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
Exclusion criteria
* Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants) * Peripheral blood blast count ≥ 50 x 103 /mm3 * Active CNS involvement with leukemia * Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide * Pregnant or nursing * Concurrently receiving any other investigational agent * Received colony stimulating factors filgrastim or sargramostim within 48 hours or pegfilgrastim within 14 days of study * Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (excluding hydroxyurea) * Severe concurrent illness that would limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML. | Days 1-42 (all patients have to complete) |
Secondary
| Measure | Time frame |
|---|---|
| To determine the safety and tolerability of plerixafor in combination with MEC | Minimum of 30 days following completion of treatment |
| To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC. | Predose, 15 min, 30 min , and 10 hrs |
| To determine the time to hematologic recovery | For up to 2 years |
| To characterize the mobilization of leukemic cells with plerixafor plus G-CSF. | Baseline, 6 hours |
| To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML. | Between days 15-42 |
| To determine the time to overall survival | For up to 2 years |
| To determine the time to event-free survival | For up to 2 years |
| To determine the time to duration of remission | For up to 2 years |
| To determine the time to relapse-free survival | For up to 2 years |
| To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts. | Baseline, 6 hours |
Countries
United States
Outcome results
None listed