AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia
AMD3100+MEC
A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML
1 other identifier
interventional
52
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2007
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2007
CompletedFirst Submitted
Initial submission to the registry
August 6, 2007
CompletedFirst Posted
Study publicly available on registry
August 7, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2010
CompletedResults Posted
Study results publicly available
September 22, 2014
CompletedDecember 12, 2016
October 1, 2016
2.9 years
August 6, 2007
July 28, 2014
October 27, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
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.
Completion of all patients in Phase I portion (232 days)
Phase II Only: Complete Response Rate of AMD3100 + MEC
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).
42 days
Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions
42 days
Secondary Outcomes (10)
Safety and Tolerability of AMD3100 + MEC.
42 days
Time to Neutrophil Recovery
42 days
Time to Platelet Recovery
42 days
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
Day 0
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
Day 0
- +5 more secondary outcomes
Study Arms (2)
Phase I Dose Escalation
EXPERIMENTAL* 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
Phase II Dose Treatment
EXPERIMENTAL* 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)
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Washington University
St Louis, Missouri, 63110, United States
Related Publications (1)
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.
PMID: 22308295DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Geoffrey L. Uy, M.D.
- Organization
- Washington University School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Geoffrey L. Uy, MD
Washington University School of Medicine
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 6, 2007
First Posted
August 7, 2007
Study Start
July 1, 2007
Primary Completion
June 1, 2010
Study Completion
June 1, 2010
Last Updated
December 12, 2016
Results First Posted
September 22, 2014
Record last verified: 2016-10