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Completed

NCT Number: NCT00512252

AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia

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.

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Key information

Conditions

Leukemia, Myeloid, Acute Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Neoplasms Neoplasms by Histologic Type

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Washington University

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Acute myeloid leukemia diagnosed by WHO criteria with one of the following:
  • Primary refractory disease following >= 1 rounds of induction chemotherapy
  • First relapse or higher
  • Age between 18 and 70 years of age
  • 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
  • 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 > 20 x 103 /mm3
  • Active CNS involvement with leukemia
  • Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
  • Pregnant or nursing
  • Receiving any other investigational agent
  • Colony stimulating factors filgrastim, pegfilgrastim or sargramostim within 2 weeks of study
  • Less than 2 weeks from the completion of any previous cytotoxic chemotherapy
  • Severe concurrent illness that would limit compliance with study requirements

Treatment and study plan

AMD3100

Drug

Other names: Plerixafor

Mitoxantrone

Drug

Other names: Novantrone

etoposide

Drug

Other names: VP-16, Vepesid, Etopophos

Cytarabine

Drug

Other names: Ara-C, Cytosar-U, Tarabine PFS

Primary outcomes

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

    Time frame: Completion of all patients in Phase I portion (232 days)

    A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 <= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity.

  2. Phase II Only: Complete Response Rate of AMD3100 + MEC

    Time frame: 42 days

    Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response.

    Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi).

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

    Time frame: 42 days

Secondary outcomes

  1. Safety and Tolerability of AMD3100 + MEC.

    Time frame: 42 days

    Treatment related mortality (deaths occurring during treatment)

  2. Time to Neutrophil Recovery

    Time frame: 42 days

    Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count >1,000 cells/mm^3.

  3. Time to Platelet Recovery

    Time frame: 42 days

    Defined as the date of the first dose of AMD3100 to the date that the platelet count is >100,000/mm3 in the absence of platelet transfusions.

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

    Time frame: Day 0

    Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.

    Characterization of the mobilized cells as well as the kinetics of mobilization will be determined by analyzing the surface expression of mobilized cells by flow cytometry at the specified time points in conjunction with their total leukocyte count from the patient's CBC.

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

    Time frame: Day 0

    Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.

  6. Pharmacokinetics of AMD3100 on MEC

    Time frame: Day 1 - Phase 2 only

  7. Time to Progression

    Time frame: Every 6 months

  8. Treatment Failure

    Time frame: 42 days

    Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.

  9. Overall Survival

    Time frame: 1 year

  10. Relapse-free Survival

    Time frame: 1 year

    This is determined only for patients achieving a complete remission. Defined as the interval from the date of the first documentation of a leukemia free state to date of recurrence or death due to any cause.

    Kaplain-Meier estimate was used.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

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

Acronym: AMD3100+MEC

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Aug 7, 2007
Registry last updated
Dec 12, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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