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Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

This study is currently recruiting participants.
Verified April 2013 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00906945
First received: May 13, 2009
Last updated: April 11, 2013
Last verified: April 2013
History of Changes
  Purpose

This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.


Condition Intervention Phase
Leukemia, Myeloid, Acute
 Drug: G-CSF
Drug: Plerixafor
Drug: Mitoxantrone
Drug: Etoposide
Drug: Cytarabine
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Phase I: To determine the maximum tolerated dose of plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML [ Time Frame: 45 days after start of treatment ] [ Designated as safety issue: Yes ]
  • Phase II: To determine the complete response rate (CR+CRi) for plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML. [ Time Frame: 45 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the safety and tolerability. [ Time Frame: 30 days following end of treatment ] [ Designated as safety issue: Yes ]
  • To determine the time to hematologic recovery [ Time Frame: 45 days after start of therapy ] [ Designated as safety issue: No ]
  • To characterize the mobilization of leukemic cells with plerixafor plus G-CSF. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts. [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • To determine time to progression [ Time Frame: Every 6 months for up to 2 years ] [ Designated as safety issue: No ]
  • Determine time to treatment failure [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Determine overall survival [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 76
Study Start Date: February 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 240 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
Experimental: Dose Level 2
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 320 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
Experimental: Dose Level 3
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 420 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
Experimental: Dose Level 4
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 560 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
Experimental: Dose Level 5
  • G-CSF 10 mcg/kg SQ on Days 1-8
  • Plerixafor 750 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
Experimental: MTD - Phase II
  • G-CSF MTD determined in Phase 1 SQ on Days 1-8
  • Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
  • Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
  • Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
  • Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
 Drug: G-CSF
Other Names:
  • filgrastim
  • Neupogen
Drug: Plerixafor
Other Names:
  • AMD3100
  • Mozobil
Drug: Mitoxantrone
Other Name: Novantrone
Drug: Etoposide
Other Names:
  • VP-16
  • Vepesid
  • Etopophos
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar

Detailed Description:

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 this study, we seek to maximize blockage of the SDF-1/CXCR4 axis through the following:

  1. Addition of G-CSF, which down regulates SDF-1 expression and acts synergistically with plerixafor in stem cell mobilization
  2. Intravenous instead of subcutaneous dosing of plerixafor to improve kinetics of administration.
  3. Dose escalation of plerixafor and twice daily dosing to maintain maximum CXCR4 blockade.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following:

    • Primary refractory disease following ≥ 1 round of induction chemotherapy
    • First relapse or higher
  2. Age between 18 and 70 years old
  3. ECOG performance status ≤ 3
  4. Adequate organ function defined as:

Calculated creatinine clearance ≥ 50 ml/min AST, ALT, total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia); Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram 5. Are surgically or biologically sterile or willing to practice acceptable birth control, as follows: i. Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence.

ii. Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period 6. 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. Received any other investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within the preceding 2 weeks
  7. Received colony stimulating factors filgrastim or sargramostim within 1 week or pegfilgrastim within 2 weeks of study
  8. Severe concurrent illness that would limit compliance with study requirements
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906945

Contacts
Contact: Geoffrey L Uy, M.D. 314-454-8304 guy@wustl.edu

Locations
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Sub-Investigator: Richard M. Stone, M.D.            
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Sub-Investigator: Karen Ballen, M.D.            
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Geoffrey L. Uy, M.D.            
Sub-Investigator: John F. DiPersio, M.D., Ph.D.            
Sub-Investigator: Peter Westervelt, M.D.,Ph.D.            
Sub-Investigator: Camille N. Abboud, M.D.            
Sub-Investigator: Amanda F. Cashen, M.D.            
Sub-Investigator: Keith E. Stockerl-Goldstein, M.D.            
Sub-Investigator: Ravi Vij, M.D.            
Sub-Investigator: Timothy J. Graubert, M.D.            
Sub-Investigator: Michael H. Tomasson, M.D.            
Sub-Investigator: Matthew J. Walter, M.D.            
Sub-Investigator: Todd A. Fehninger, M.D., Ph.D.            
Sub-Investigator: Mark Schroeder, M.D.            
Sub-Investigator: Giridharan Ramsingh, M.D.            
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sub-Investigator: Marina Konopleva, M.D., Ph.D.            
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Geoffrey L. Uy, M.D. Washington University School of Medicine
  More Information

Additional Information:
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00906945     History of Changes
Other Study ID Numbers: 10-0910 / 201106039
Study First Received: May 13, 2009
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
stem cell mobilization
chemosensitization
CXCR4
SDF-1
CXCL-12

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
JM 3100
Etoposide phosphate
Etoposide
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
 Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on May 21, 2013