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AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia

Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia, Myeloid, Acute

Intervention: AMD3100 (Drug); Mitoxantrone (Drug); Etoposide (Drug); Cytarabine (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Washington University School of Medicine

Official(s) and/or principal investigator(s):
Geoffrey L. Uy, MD, Principal Investigator, Affiliation: Washington University School of Medicine


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.

Clinical Details

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

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

Primary outcome:

Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML

Phase II Only: Complete Response Rate of AMD3100 + MEC

Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions

Secondary outcome:

Safety and Tolerability of AMD3100 + MEC.

Time to Neutrophil Recovery

Time to Platelet Recovery

Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)

Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)

Pharmacokinetics of AMD3100 on MEC

Time to Progression

Treatment Failure

Overall Survival

Relapse-free Survival

Detailed description: 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.


Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.


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

Locations and Contacts

Washington University, St. Louis, Missouri 63110, United States
Additional Information

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Starting date: July 2007
Last updated: September 12, 2014

Page last updated: August 23, 2015

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