Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

NCT ID: NCT00906945

Last Updated: 2017-04-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2015-09-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Leukemia, Myeloid, Acute

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Level 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

MTD - Phase II

* 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

Group Type EXPERIMENTAL

G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Interventions

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G-CSF

Intervention Type DRUG

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Other Intervention Names

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filgrastim Neupogen AMD3100 Mozobil Novantrone VP-16 Vepesid Etopophos Ara-C Cytosar

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey L. Uy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

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10-0910 / 201106039

Identifier Type: -

Identifier Source: org_study_id

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