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

Primary Purpose

Leukemia, Myeloid, Acute

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Plerixafor
Mitoxantrone
Etoposide
Cytarabine
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.

Secondary Outcome Measures

To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.
To determine the safety and tolerability of plerixafor in combination with MEC
To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.
To determine the time to hematologic recovery
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
To determine the time to overall survival
To determine the time to event-free survival
To determine the time to duration of remission
To determine the time to relapse-free survival

Full Information

First Posted
December 7, 2009
Last Updated
January 21, 2015
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01027923
Brief Title
IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)
Acronym
AML
Official Title
A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Terminated
Why Stopped
Withdrawal of support from sponsor
Study Start Date
May 2010 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1
Arm Type
Experimental
Arm Description
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
Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
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
Arm Title
Dose Level 3
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Other Intervention Name(s)
AMD3100, Mozobil
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Novantrone
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Etopophos, Toposar, VePesid, VP156
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Cytosar-U, Ara-C, Cytosine arabinoside
Primary Outcome Measure Information:
Title
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)
Secondary Outcome Measure Information:
Title
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
Title
To determine the safety and tolerability of plerixafor in combination with MEC
Time Frame
Minimum of 30 days following completion of treatment
Title
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
Title
To determine the time to hematologic recovery
Time Frame
For up to 2 years
Title
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
Time Frame
Baseline, 6 hours
Title
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
Time Frame
Baseline, 6 hours
Title
To determine the time to overall survival
Time Frame
For up to 2 years
Title
To determine the time to event-free survival
Time Frame
For up to 2 years
Title
To determine the time to duration of remission
Time Frame
For up to 2 years
Title
To determine the time to relapse-free survival
Time Frame
For up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geoffrey Uy, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Links:
URL
http://siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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

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