AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia (AMD3100+MEC)
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|ClinicalTrials.gov Identifier: NCT00512252|
Recruitment Status : Completed
First Posted : August 7, 2007
Results First Posted : September 22, 2014
Last Update Posted : December 12, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myeloid, Acute||Drug: AMD3100 Drug: Mitoxantrone Drug: Etoposide Drug: Cytarabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||June 2010|
Experimental: Phase I Dose Escalation
Dose Level 1 AMD3100 dose = 80 mcg/kg/d
Dose Level 2 AMD3100 dose = 160 mcg/kg/d
Other Name: Plerixafor
Other Name: Novantrone
Experimental: Phase II Dose Treatment
Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose)
Other Name: Plerixafor
Other Name: Novantrone
- 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.
- 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).
- Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions [ Time Frame: 42 days ]
- Safety and Tolerability of AMD3100 + MEC. [ Time Frame: 42 days ]Treatment related mortality (deaths occurring during treatment)
- 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.
- 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.
- 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.
- 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.
- Pharmacokinetics of AMD3100 on MEC [ Time Frame: Day 1 - Phase 2 only ]
- Time to Progression [ Time Frame: Every 6 months ]
- Treatment Failure [ Time Frame: 42 days ]Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.
- Overall Survival [ Time Frame: 1 year ]
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00512252
|United States, Missouri|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Geoffrey L. Uy, MD||Washington University School of Medicine|