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A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML

Phase 1/Phase 2
18 Years
70 Years
Not Enrolling
Leukemia, Myeloid, Acute

Thank you

Trial Information

A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML

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.

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the optimal dose and schedule of AMD3100 plus MEC in patients with relapsed or refractory AML

Outcome Time Frame:

Length of Phase I

Safety Issue:


Principal Investigator

Geoffrey L. Uy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Food and Drug Administration

Study ID:

07-0227 / 201011796



Start Date:

July 2007

Completion Date:

June 2010

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Plerixafor
  • CXCR4
  • Chemosensitization
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Washington University St. Louis, Missouri  63110