AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia (AMD3100+MEC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00512252
First received: August 6, 2007
Last updated: April 25, 2014
Last verified: April 2014

August 6, 2007
April 25, 2014
July 2007
June 2010   (final data collection date for primary outcome measure)
  • Phase I only: optimal dose and schedule of AMD3100 plus MEC in patients with relapsed or refractory AML [ Time Frame: Completion of all patients in Phase I portion ] [ Designated as safety issue: Yes ]
  • Phase II only: complete response rate of AMD3100 + MEC [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Ability of AMD3100 + MEC to induce dsDNA damage and apoptosis in leukemic blasts from bone marrow or peripheral blood fractions [ Time Frame: 42 days ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00512252 on ClinicalTrials.gov Archive Site
  • Safety and tolerability of AMD3100 + MEC. [ Time Frame: 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
  • Time to hematologic recovery [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Characterize the mobilization of leukemic cells with AMD3100 [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of AMD3100 on MEC [ Time Frame: Day 1 - Phase 2 only ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia
A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML

This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML.

We hypothesize that disrupting the interaction between AML blasts and the marrow microenvironment with AMD3100 may enhance the cytotoxic effect of chemotherapy.

The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although a number of receptor / ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being developed clinically as a mobilization agent for hematopoietic stem cell transplantation. Preclinical data from our group has demonstrated that in murine models, plerixafor can disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II study in patients with relapsed or refractory AML in which plerixafor is administered prior to salvage chemotherapy.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia, Myeloid, Acute
  • Drug: AMD3100
    Other Name: Plerixafor
  • Drug: Mitoxantrone
    Other Name: Novantrone
  • Drug: Etoposide
    Other Names:
    • VP-16
    • Vepesid
    • Etopophos
  • Drug: Cytarabine
    Other Names:
    • Ara-C
    • Cytosar-U
    • Tarabine PFS
  • Experimental: Dose Level 1
    • AMD 3100 80 mcg/kg SQ on days 0-5
    • Mitoxantrone 8 mg/m2 on days 1-5
    • Etoposide 100 mg/m2 on days 1-5
    • Cytarabine 1000 mg/m2 on days 1-5
    Interventions:
    • Drug: AMD3100
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
  • Experimental: Dose Level 2
    • AMD 3100 160 mcg/kg SQ on days 0-5
    • Mitoxantrone 8 mg/m2 on days 1-5
    • Etoposide 100 mg/m2 on days 1-5
    • Cytarabine 1000 mg/m2 on days 1-5
    Interventions:
    • Drug: AMD3100
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
  • Experimental: Dose Level 3
    • AMD 3100 240 mcg/kg SQ on days 0-5
    • Mitoxantrone 8 mg/m2 on days 1-5
    • Etoposide 100 mg/m2 on days 1-5
    • Cytarabine 1000 mg/m2 on days 1-5
    Interventions:
    • Drug: AMD3100
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
  • Experimental: Phase II
    • AMD 3100 (dose determined in Phase I) SQ on days 0-5
    • Mitoxantrone 8 mg/m2 on days 1-5
    • Etoposide 100 mg/m2 on days 1-5
    • Cytarabine 1000 mg/m2 on days 1-5
    Interventions:
    • Drug: AMD3100
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, Kulkarni S, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Vij R, Westervelt P, DiPersio JF. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 2012 Apr 26;119(17):3917-24. doi: 10.1182/blood-2011-10-383406. Epub 2012 Feb 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
June 2010
June 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following:

    1. Primary refractory disease following >= 1 rounds of induction chemotherapy
    2. First relapse or higher
  2. Age between 18 and 70 years of age
  3. Adequate organ function defined as Creatinine <= 1.5 x institutional ULN; AST, ALT, total bilirubin <= 2 x ULN; Left ventricular ejection fraction of >= 40% by MUGA scan
  4. Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study
  5. 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. Receiving any other investigational agent
  7. Colony stimulating factors filgrastim, pegfilgrastim or sargramostim within 2 weeks of study
  8. Less than 2 weeks from the completion of any previous cytotoxic chemotherapy
  9. Severe concurrent illness that would limit compliance with study requirements
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00512252
07-0227 / 201011796
No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Geoffrey L. Uy, MD Washington University Early Recognition Center
Washington University School of Medicine
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP