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

January 21, 2015 updated by: Washington University School of Medicine

A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Names:
  • Novantrone
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar-U
  • Cytosine arabinoside
Drug: Etoposide
Other Names:
  • Toposar
  • Etopophos
  • VePesid
  • VP156
Experimental: 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
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Names:
  • Novantrone
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar-U
  • Cytosine arabinoside
Drug: Etoposide
Other Names:
  • Toposar
  • Etopophos
  • VePesid
  • VP156
Experimental: 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
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Names:
  • Novantrone
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar-U
  • Cytosine arabinoside
Drug: Etoposide
Other Names:
  • Toposar
  • Etopophos
  • VePesid
  • VP156

What is the study measuring?

Primary Outcome Measures

Outcome 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.
Time Frame: Days 1-42 (all patients have to complete)
Days 1-42 (all patients have to complete)

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.
Time Frame: Between days 15-42
Between days 15-42
To determine the safety and tolerability of plerixafor in combination with MEC
Time Frame: Minimum of 30 days following completion of treatment
Minimum of 30 days following completion of treatment
To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.
Time Frame: Predose, 15 min, 30 min , and 10 hrs
Predose, 15 min, 30 min , and 10 hrs
To determine the time to hematologic recovery
Time Frame: For up to 2 years
For up to 2 years
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
Time Frame: Baseline, 6 hours
Baseline, 6 hours
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
Time Frame: Baseline, 6 hours
Baseline, 6 hours
To determine the time to overall survival
Time Frame: For up to 2 years
For up to 2 years
To determine the time to event-free survival
Time Frame: For up to 2 years
For up to 2 years
To determine the time to duration of remission
Time Frame: For up to 2 years
For up to 2 years
To determine the time to relapse-free survival
Time Frame: For up to 2 years
For up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

December 7, 2009

First Submitted That Met QC Criteria

December 8, 2009

First Posted (Estimate)

December 9, 2009

Study Record Updates

Last Update Posted (Estimate)

January 26, 2015

Last Update Submitted That Met QC Criteria

January 21, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-1825 / 201101703

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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