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IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01027923
First received: December 7, 2009
Last updated: August 9, 2013
Last verified: August 2013

December 7, 2009
August 9, 2013
May 2010
July 2010   (final data collection date for primary outcome measure)
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML. [ Time Frame: Days 1-42 (all patients have to complete) ] [ Designated as safety issue: Yes ]
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01027923 on ClinicalTrials.gov Archive Site
  • To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML. [ Time Frame: Between days 15-42 ] [ Designated as safety issue: No ]
  • To determine the safety and tolerability of plerixafor in combination with MEC [ Time Frame: Minimum of 30 days following completion of treatment ] [ Designated as safety issue: Yes ]
  • To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC. [ Time Frame: Predose, 15 min, 30 min , and 10 hrs ] [ Designated as safety issue: No ]
  • To determine the time to hematologic recovery [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
  • To characterize the mobilization of leukemic cells with plerixafor plus G-CSF. [ Time Frame: Baseline, 6 hours ] [ Designated as safety issue: No ]
  • To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts. [ Time Frame: Baseline, 6 hours ] [ Designated as safety issue: No ]
  • To determine the time to overall survival [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
  • To determine the time to event-free survival [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
  • To determine the time to duration of remission [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
  • To determine the time to relapse-free survival [ Time Frame: For up to 2 years ] [ Designated as safety issue: No ]
  • To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To determine the safety and tolerability of plerixafor in combination with MEC [ Time Frame: 1 years ] [ Designated as safety issue: Yes ]
  • To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To determine the time to hematologic recovery, overall survival, event-free survival, duration of remission,relapse-free survival, and overall survival. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To characterize the mobilization of leukemic cells with plerixafor plus G-CSF. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)
A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia

In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.

In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia, Myeloid, Acute
  • Drug: Plerixafor
    Other Names:
    • AMD3100
    • Mozobil
  • Drug: Mitoxantrone
    Other Name: Novantrone
  • Drug: Etoposide
    Other Names:
    • Etopophos
    • Toposar
    • VePesid
    • VP156
  • Drug: Cytarabine
    Other Names:
    • Cytosar-U
    • Ara-C
    • Cytosine arabinoside
  • Experimental: Dose Level 1

    Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

    Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5

    Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

    Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

    Interventions:
    • Drug: Plerixafor
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
  • Experimental: Dose Level 2

    Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

    Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5

    Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

    Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

    Interventions:
    • Drug: Plerixafor
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
  • Experimental: Dose Level 3

    Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5

    Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5

    Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5

    Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

    Interventions:
    • Drug: Plerixafor
    • Drug: Mitoxantrone
    • Drug: Etoposide
    • Drug: Cytarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
September 2011
July 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:

    • Primary refractory disease following ≥ 1 round of induction chemotherapy
    • First relapse or higher
  • Age between 18 and 70 years
  • ECOG performance status ≤ 2
  • Adequate organ function defined as:

    • Creatinine ≤ 1.5 x institutional ULN
    • AST ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
    • ALT ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
    • Total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
    • Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
  • 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 ≥ 50 x 103 /mm3
  • Active CNS involvement with leukemia
  • Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
  • Pregnant or nursing
  • Concurrently receiving any other investigational agent
  • Received colony stimulating factors filgrastim or sargramostim within 48 hours or pegfilgrastim within 14 days of study
  • Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (excluding hydroxyurea)
  • Severe concurrent illness that would limit compliance with study requirements
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01027923
09-1825 / 201101703
No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Geoffrey Uy, M.D. Washington University School of Medicine
Washington University School of Medicine
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP