IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)

NCT ID: NCT01027923

Last Updated: 2015-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2011-09-30

Brief Summary

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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

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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 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.

Conditions

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Leukemia, Myeloid, Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Level 1

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5

Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 2

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5

Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Dose Level 3

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5

Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Group Type EXPERIMENTAL

Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Interventions

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Plerixafor

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Other Intervention Names

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AMD3100 Mozobil Novantrone Etopophos Toposar VePesid VP156 Cytosar-U Ara-C Cytosine arabinoside

Eligibility Criteria

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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
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 Uy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

Related Links

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http://siteman.wustl.edu

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

Other Identifiers

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09-1825 / 201101703

Identifier Type: -

Identifier Source: org_study_id

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