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AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia

NCT ID: NCT00512252

Last Updated: 2016-12-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia, Myeloid, Acute

Keywords

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Plerixafor CXCR4 Chemosensitization

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I Dose Escalation

* AMD3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5

Dose Level 1 AMD3100 dose = 80 mcg/kg/d

Dose Level 2 AMD3100 dose = 160 mcg/kg/d

Group Type EXPERIMENTAL

AMD3100

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Phase II Dose Treatment

* AMD 3100 SQ on days 0-5
* Mitoxantrone on days 1-5
* Etoposide on days 1-5
* Cytarabine on days 1-5

Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose)

Group Type EXPERIMENTAL

AMD3100

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Interventions

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AMD3100

Intervention Type DRUG

Mitoxantrone

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Other Intervention Names

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Plerixafor Novantrone VP-16 Vepesid Etopophos Ara-C Cytosar-U Tarabine PFS

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey L. Uy, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 22308295 (View on PubMed)

Related Links

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http://www.siteman.wustl.edu

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

Other Identifiers

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07-0227 / 201011796

Identifier Type: -

Identifier Source: org_study_id