Overview

This trial is active, not recruiting.

Condition leukemia, myeloid, acute
Treatments g-csf, plerixafor, mitoxantrone, etoposide, cytarabine
Phase phase 1/phase 2
Sponsor Washington University School of Medicine
Start date February 2011
End date November 2012
Trial size 39 participants
Trial identifier NCT00906945, 10-0910 / 201106039

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C
(Experimental)
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
g-csf filgrastim
plerixafor AMD3100
mitoxantrone Novantrone
etoposide VP-16
cytarabine Ara-C

Primary Outcomes

Measure
Phase I: To determine the maximum tolerated dose of plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML
time frame: 45 days after start of treatment
Phase II: To determine the complete response rate (CR+CRi) for plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML.
time frame: 45 days

Secondary Outcomes

Measure
To determine the safety and tolerability.
time frame: 30 days following end of treatment
To determine the time to hematologic recovery
time frame: 45 days after start of therapy
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
time frame: 8 days
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
time frame: 8 days
To determine time to progression
time frame: Every 6 months for up to 2 years
Determine time to treatment failure
time frame: 8 days
Determine overall survival
time frame: Every 6 months for 2 years

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

Inclusion Criteria: 1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following: - Primary refractory disease following no more than 2 cycles of induction chemotherapy - First relapse with no prior unsuccessful salvage chemotherapy 2. Age between 18 and 70 years old 3. ECOG performance status ≤ 3 4. Adequate organ function defined as: - Calculated creatinine clearance ≥ 50 ml/min - AST, ALT, total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia) - Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram 5. Are surgically or biologically sterile or willing to practice acceptable birth control, as follows: - Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence. - Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period 6. Able to provide signed informed consent prior to registration on study Exclusion Criteria: 1. Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants) 2. Peripheral blood blast count ≥ 20 x 103 /mm3 3. Active CNS involvement with leukemia 4. Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide 5. Pregnant or nursing 6. Received any other investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within the preceding 2 weeks 7. Received colony stimulating factors filgrastim or sargramostim within 1 week or pegfilgrastim within 2 weeks of study 8. Severe concurrent illness that would limit compliance with study requirements

Additional Information

Official title Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia
Principal investigator Geoffrey L. Uy, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Washington University School of Medicine.