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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01027923
First received: December 7, 2009
Last updated: February 19, 2013
Last verified: February 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Leukemia, Myeloid, Acute
 Drug: Plerixafor
Drug: Mitoxantrone
Drug: Etoposide
Drug: Cytarabine
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

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. [ Time Frame: Days 1-42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • To determine the safety and tolerability of plerixafor in combination with MEC [ Time Frame: Days 1-42 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To determine the time to hematologic recovery, overall survival, event-free survival, duration of remission, relapse-free survival, and overall survival. [ Time Frame: Until event ] [ Designated as safety issue: No ]
  • To characterize the mobilization of leukemic cells with plerixafor plus G-CSF. [ Time Frame: Baseline, 6 hours ] [ Designated as safety issue: No ]
  • To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts. [ Time Frame: Baseline, 6 hours ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: May 2010
Study Completion Date: September 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level -1
Mitoxantrone + Etoposide + Cytarabine + Plerixafor 240 mcg/kg/day IV
 Drug: Plerixafor
Plerixafor IV 240-560 mcg/kg/day IV on Days 0 thru Day 5
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Mitoxantrone 8 mg/m2/day IV on Days 1 thru 5 starting 4-5 hours after plerixafor
Other Name: Novantrone
Drug: Etoposide
Etoposide 100 mg/m2/day IV on over 60 minutes once daily on Days 1 thru 5
Other Names:
  • Etopophos
  • Toposar
  • VePesid
  • VP156
Drug: Cytarabine
Cytarabine 1,000 mg/m2/day IV over 60 minutes once daily on days 1-5
Other Names:
  • Cytosar-U
  • Ara-C
  • Cytosine arabinoside
Experimental: Dose Level 1
Mitoxantrone + Etoposide + Cytarabine + Plerixafor 320 mcg/kg/day IV
 Drug: Plerixafor
Plerixafor IV 240-560 mcg/kg/day IV on Days 0 thru Day 5
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Mitoxantrone 8 mg/m2/day IV on Days 1 thru 5 starting 4-5 hours after plerixafor
Other Name: Novantrone
Drug: Etoposide
Etoposide 100 mg/m2/day IV on over 60 minutes once daily on Days 1 thru 5
Other Names:
  • Etopophos
  • Toposar
  • VePesid
  • VP156
Drug: Cytarabine
Cytarabine 1,000 mg/m2/day IV over 60 minutes once daily on days 1-5
Other Names:
  • Cytosar-U
  • Ara-C
  • Cytosine arabinoside
Experimental: Dose Level 2
Mitoxantrone + Etoposide + Cytarabine + Plerixafor 420 mcg/kg/day IV
 Drug: Plerixafor
Plerixafor IV 240-560 mcg/kg/day IV on Days 0 thru Day 5
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Mitoxantrone 8 mg/m2/day IV on Days 1 thru 5 starting 4-5 hours after plerixafor
Other Name: Novantrone
Drug: Etoposide
Etoposide 100 mg/m2/day IV on over 60 minutes once daily on Days 1 thru 5
Other Names:
  • Etopophos
  • Toposar
  • VePesid
  • VP156
Drug: Cytarabine
Cytarabine 1,000 mg/m2/day IV over 60 minutes once daily on days 1-5
Other Names:
  • Cytosar-U
  • Ara-C
  • Cytosine arabinoside
Experimental: Dose Level 3
Mitoxantrone + Etoposide + Cytarabine + Plerixafor 560 mcg/kg/day IV
 Drug: Plerixafor
Plerixafor IV 240-560 mcg/kg/day IV on Days 0 thru Day 5
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Mitoxantrone 8 mg/m2/day IV on Days 1 thru 5 starting 4-5 hours after plerixafor
Other Name: Novantrone
Drug: Etoposide
Etoposide 100 mg/m2/day IV on over 60 minutes once daily on Days 1 thru 5
Other Names:
  • Etopophos
  • Toposar
  • VePesid
  • VP156
Drug: Cytarabine
Cytarabine 1,000 mg/m2/day IV over 60 minutes once daily on days 1-5
Other Names:
  • Cytosar-U
  • Ara-C
  • Cytosine arabinoside

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01027923

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Geoffrey Uy, M.D. Washington University School of Medicine
  More Information

Additional Information:
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01027923     History of Changes
Other Study ID Numbers: 09-1825 / 201101703
Study First Received: December 7, 2009
Last Updated: February 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
JM 3100
Etoposide phosphate
Etoposide
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
 Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on May 16, 2013