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Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT00906945
Collaborator
(none)
39
Enrollment
3
Locations
6
Arms
55
Duration (Months)
13
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia
Study Start Date :
Feb 1, 2011
Actual Primary Completion Date :
Nov 1, 2012
Actual Study Completion Date :
Sep 1, 2015

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Novantrone

    • Drug: Etoposide
    Other Names:
  • VP-16
  • Vepesid
  • Etopophos

    • Drug: Cytarabine
    Other Names:
  • Ara-C
  • Cytosar

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC [Completion of Phase I enrollment (17 months)]

    2. Phase II: Complete Response Rate (CR+CRi) [45 days]

      Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1,000/mm3, platelet count > 100,000/mm3. Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1,000/mm3 or thrombocytopenia <100,000/mm3.

    Secondary Outcome Measures

    1. Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency [30 days following end of treatment]

    2. Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery [Up to 62 days after treatment]

      -Neutrophil recovery is defined as absolute neutrophil count (ANC) >= 500/mm^3

    3. Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery [Up to 62 days after treatment]

      -Neutrophil recovery is defined as absolute neutrophil count >= 1000/mm^3

    4. Time to Hematologic Recovery as Measured by Time to Platelet Recovery [Up to 62 days after treatment]

      -Platelet recovery is defined as platelets >= 50,000/mm^3

    5. Time to Hematologic Recovery as Measured by Time to Platelet Recovery [Up to 62 days after treatment]

      -Platelet recovery is defined as platelets >= 100,000/mm3

    6. Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells [6 hours after plerixafor]

    7. Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count [6 hours after plerixafor]

    8. Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity [6 hours after plerixafor]

    9. Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity [6 hours after plerixafor]

    10. Time to Progression [2 years]

      Recurrence / morphologic relapse: Defined as reappearance of blasts in the blood or the finding of > 5% blasts in the BM, not attributable to any other cause. New dysplastic changes are considered a relapse. If there are no blasts in the peripheral blood and 5-19% blasts in the BM, the BM biopsy and aspirate should be repeated in > 1 week to confirm relapse.

    11. Time to Treatment Failure [8 days]

    12. Overall Survival [Median follow-up was 34.6 months]

      Overall survival: Defined as the date of first dose of study drug to the date of death from any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following:

    • Primary refractory disease following no more than 2 cycles of induction chemotherapy

    • First relapse with no prior unsuccessful salvage chemotherapy

    1. Age between 18 and 70 years old

    2. ECOG performance status ≤ 3

    3. 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

    1. Are surgically or biologically sterile or willing to practice acceptable birth control, as follows:

    • 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.

    • 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

    1. 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

    Locations

    Site City State Country Postal Code
    1 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    2 Washington University St. Louis Missouri United States 63110
    3 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Geoffrey L. Uy, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00906945
    Other Study ID Numbers:
    • 10-0910 / 201106039
    First Posted:
    May 21, 2009
    Last Update Posted:
    Apr 4, 2017
    Last Verified:
    Feb 1, 2017
    Keywords provided by Washington University School of Medicine
    stem cell mobilization
    chemosensitization
    CXCR4
    SDF-1
    CXCL-12
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Cytarabine
    Plerixafor
    Etoposide
    Mitoxantrone

    Study Results

    Participant Flow

    Recruitment Details The study opened to participant enrollment on 02/04/2011 and closed to participant enrollment on 08/19/2013.
    Pre-assignment Detail
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 MTD - Phase II
    Arm/Group Description 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 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 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 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 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 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
    Period Title: Overall Study
    STARTED 3 3 3 7 7 16
    COMPLETED 3 3 3 6 6 14
    NOT COMPLETED 0 0 0 1 1 2

    Baseline Characteristics

    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 (Includes MTD-Phase II) Total
    Arm/Group Description 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 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 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 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 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 Total of all reporting groups
    Overall Participants 3 3 3 6 20 35
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    63
    47
    64
    54
    56
    56
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    2
    66.7%
    1
    33.3%
    4
    66.7%
    8
    40%
    17
    48.6%
    Male
    1
    33.3%
    1
    33.3%
    2
    66.7%
    2
    33.3%
    12
    60%
    18
    51.4%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    20
    100%
    35
    100%

    Outcome Measures

    1. Primary Outcome
    Title Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC
    Description
    Time Frame Completion of Phase I enrollment (17 months)

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed is the number of participants enrolled in the Phase I portion of the study.
    Arm/Group Title Phase I (Includes Levels 1-5)
    Arm/Group Description
    Measure Participants 21
    Number [mcg/kg/day]
    750
    2. Primary Outcome
    Title Phase II: Complete Response Rate (CR+CRi)
    Description Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1,000/mm3, platelet count > 100,000/mm3. Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1,000/mm3 or thrombocytopenia <100,000/mm3.
    Time Frame 45 days

    Outcome Measure Data

    Analysis Population Description
    Only patients enrolled in Phase 2 portion were analyzed for this outcome measure.
    Arm/Group Title Phase II (MTD)
    Arm/Group Description
    Measure Participants 20
    Number [percentage of participants]
    30
    1000%
    3. Secondary Outcome
    Title Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
    Description
    Time Frame 30 days following end of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
    Arm/Group Description
    Measure Participants 35 35 35 35 35
    Anemia
    0
    4
    9
    0
    0
    Febrile neutropenia
    0
    0
    20
    0
    0
    Abdominal pain
    6
    0
    1
    0
    0
    Constipation
    5
    2
    0
    0
    0
    Diarrhea
    7
    6
    0
    0
    0
    Gastroesophageal reflux disease
    1
    5
    0
    0
    0
    Mucositis oral
    2
    3
    1
    0
    0
    Nausea
    21
    3
    0
    0
    0
    Vomiting
    12
    0
    1
    0
    0
    Chills
    5
    0
    0
    0
    0
    Edema-limbs
    5
    1
    0
    0
    0
    Fatigue
    9
    2
    1
    0
    0
    Fever
    6
    4
    0
    0
    0
    Non-cardiac chest pain
    1
    2
    1
    0
    0
    Pain
    2
    2
    0
    0
    0
    Bacteremia
    0
    0
    4
    0
    0
    Lung infection
    0
    1
    5
    0
    2
    Sepsis
    0
    0
    0
    4
    4
    Activated partial thromboplastin time prolonged
    5
    0
    0
    0
    0
    Alanine aminotransferase increased
    3
    0
    1
    0
    0
    Alkaline phosphatase increased
    3
    1
    0
    0
    0
    Aspartate aminotransferase increased
    4
    0
    0
    0
    0
    Blood bilirubin increased
    2
    3
    1
    0
    0
    INR increased
    7
    0
    0
    0
    0
    Neutrophil count decreased
    0
    0
    0
    7
    0
    Platelet count decreased
    0
    0
    0
    15
    0
    White blood cell count decreased
    0
    0
    0
    16
    0
    Anorexia
    4
    2
    0
    0
    0
    Hypoalbuminemia
    3
    6
    0
    0
    0
    Hypocalcemia
    2
    11
    0
    0
    0
    Hypokalemia
    5
    2
    2
    2
    0
    Hypomagnesemia
    7
    0
    0
    0
    0
    Hyponatremia
    4
    0
    1
    0
    0
    Bone pain
    4
    2
    2
    0
    0
    Dizziness
    4
    1
    0
    0
    0
    Headache
    7
    6
    1
    0
    0
    Paresthesia
    4
    1
    0
    0
    0
    Insomnia
    5
    2
    0
    0
    0
    Proteinuria
    3
    1
    0
    0
    0
    Cough
    3
    2
    0
    0
    0
    Dyspnea
    3
    3
    0
    0
    0
    Pneumonitis
    1
    3
    0
    0
    1
    Rash maculo-papular
    3
    3
    0
    0
    0
    Hypotension
    4
    4
    2
    0
    0
    4. Secondary Outcome
    Title Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
    Description -Neutrophil recovery is defined as absolute neutrophil count (ANC) >= 500/mm^3
    Time Frame Up to 62 days after treatment

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi whose ANC was >=500/mm^3 were evaluable for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 9
    Median (Full Range) [days]
    38
    5. Secondary Outcome
    Title Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
    Description -Neutrophil recovery is defined as absolute neutrophil count >= 1000/mm^3
    Time Frame Up to 62 days after treatment

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi whose ANC was >=1000/mm^3 were evaluable for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 8
    Median (Full Range) [days]
    40
    6. Secondary Outcome
    Title Time to Hematologic Recovery as Measured by Time to Platelet Recovery
    Description -Platelet recovery is defined as platelets >= 50,000/mm^3
    Time Frame Up to 62 days after treatment

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study (both Phase I or Phase II) who had CR whose platelets were >=50,000/mm^3 were evaluable for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 9
    Median (Full Range) [days]
    32
    7. Secondary Outcome
    Title Time to Hematologic Recovery as Measured by Time to Platelet Recovery
    Description -Platelet recovery is defined as platelets >= 100,000/mm3
    Time Frame Up to 62 days after treatment

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study (both Phase I or Phase II) who had a CR whose platelets were >=100,000/mm^3 were evaluable for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 7
    Median (Full Range) [days]
    32
    8. Secondary Outcome
    Title Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells
    Description
    Time Frame 6 hours after plerixafor

    Outcome Measure Data

    Analysis Population Description
    31 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 4 patients did not have usable peripheral blood samples for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 31
    Mean (Standard Deviation) [fold change in white blood cells]
    4.6
    (3.6)
    9. Secondary Outcome
    Title Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count
    Description
    Time Frame 6 hours after plerixafor

    Outcome Measure Data

    Analysis Population Description
    31 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 4 patients did not have usable peripheral blood samples for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 31
    Mean (Standard Deviation) [fold change in AML blast count]
    9.4
    (11.6)
    10. Secondary Outcome
    Title Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity
    Description
    Time Frame 6 hours after plerixafor

    Outcome Measure Data

    Analysis Population Description
    29 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 6 patients did not have usable peripheral blood samples for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 29
    Mean (Standard Deviation) [fold change in CXCR4 clone 1D9]
    8.0
    (13.2)
    11. Secondary Outcome
    Title Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity
    Description
    Time Frame 6 hours after plerixafor

    Outcome Measure Data

    Analysis Population Description
    29 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 6 patients did not have usable peripheral blood samples for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 29
    Mean (Standard Deviation) [fold change in CXCR4 clone 1D9]
    0.9
    (0.9)
    12. Secondary Outcome
    Title Time to Progression
    Description Recurrence / morphologic relapse: Defined as reappearance of blasts in the blood or the finding of > 5% blasts in the BM, not attributable to any other cause. New dysplastic changes are considered a relapse. If there are no blasts in the peripheral blood and 5-19% blasts in the BM, the BM biopsy and aspirate should be repeated in > 1 week to confirm relapse.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome measure. Progression is very hard to define acute myeloid leukemia and including it as a pre-specified secondary outcome measure in the protocol was an oversight.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 0
    13. Secondary Outcome
    Title Time to Treatment Failure
    Description
    Time Frame 8 days

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome measure. It is not well defined in the literature as when to measure treatment failure. Relapse free survival is a better way to measure response duration (this outcome measure was added to the results).
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 0
    14. Secondary Outcome
    Title Overall Survival
    Description Overall survival: Defined as the date of first dose of study drug to the date of death from any cause.
    Time Frame Median follow-up was 34.6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 35
    Median (Full Range) [days]
    227
    15. Post-Hoc Outcome
    Title Relapse Free-survival Rate
    Description
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi were evaluable for this outcome measure.
    Arm/Group Title Phase I and Phase II Participants
    Arm/Group Description
    Measure Participants 9
    Number [percentage of participants]
    75
    2500%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 MTD - Phase II
    Arm/Group Description 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 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 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 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 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 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
    All Cause Mortality
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 MTD - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 MTD - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 2/6 (33.3%) 2/6 (33.3%) 2/14 (14.3%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Cardiac disorders
    Cardiac troponin increased 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Infections and infestations
    Lung infection 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Sepsis 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 1/14 (7.1%)
    Musculoskeletal and connective tissue disorders
    Body pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Bone pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Vascular disorders
    Hypotension 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Subdural hematoma 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Other (Not Including Serious) Adverse Events
    Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 MTD - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 6/6 (100%) 14/14 (100%)
    Blood and lymphatic system disorders
    Anemia 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 9/14 (64.3%)
    Leukocytosis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Sinus bradycardia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Sinus tachycardia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Congenital, familial and genetic disorders
    Double uterus 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Eye disorders
    Blurred vision 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Floaters 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Subconjunctival hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Gastrointestinal disorders
    Abdominal cramping 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Abdominal pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 3/6 (50%) 2/6 (33.3%) 1/14 (7.1%)
    Bloating 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Constipation 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 2/6 (33.3%) 1/14 (7.1%)
    Diarrhea 1/3 (33.3%) 1/3 (33.3%) 2/3 (66.7%) 3/6 (50%) 2/6 (33.3%) 4/14 (28.6%)
    Dry mouth 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Dyspepsia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Dysphagia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Esophageal pain 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Fecal incontinence 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Gastroesophageal reflux disease 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Mucositis oral 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 2/6 (33.3%) 0/14 (0%)
    Nausea 2/3 (66.7%) 1/3 (33.3%) 3/3 (100%) 5/6 (83.3%) 5/6 (83.3%) 8/14 (57.1%)
    Oral dysesthesia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Oral hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Oral pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Perirectal abscess 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Perirectal pain 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Rectal pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Rectal ulcer 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Stomach pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Vomiting 0/3 (0%) 1/3 (33.3%) 2/3 (66.7%) 3/6 (50%) 3/6 (50%) 4/14 (28.6%)
    General disorders
    Chills 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 0/6 (0%) 1/14 (7.1%)
    Edema: limbs 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 1/6 (16.7%) 2/14 (14.3%)
    Fatigue 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 4/6 (66.7%) 2/6 (33.3%) 1/14 (7.1%)
    Fever 0/3 (0%) 0/3 (0%) 3/3 (100%) 5/6 (83.3%) 1/6 (16.7%) 1/14 (7.1%)
    Graft versus host disease 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Non-cardiac chest pain 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Pain 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/14 (0%)
    Immune system disorders
    Allergic reaction 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Infections and infestations
    Fungemia - Candida parapsilosis 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Bacteremia - Corynebacterium Species 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Bacteremia - Klebsiella 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Bacteremia - Staphylococcus epidermis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Bacteremia - Streptococcus agalactiae 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Enterocolitis infectious 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Febrile neutropenia 3/3 (100%) 2/3 (66.7%) 0/3 (0%) 2/6 (33.3%) 4/6 (66.7%) 8/14 (57.1%)
    Lip infection 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Lung infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/6 (33.3%) 3/14 (21.4%)
    Sepsis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 4/14 (28.6%)
    Skin infection 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Urinary tract infection 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Investigations
    Activated partial thromboplastin time prolonged 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Alanine aminotransferase increased 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Alkaline phosphatase increased 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 3/14 (21.4%)
    Aspartate aminotransferase increased 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 2/14 (14.3%)
    Blood bilirubin increased 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 3/14 (21.4%)
    INR increased 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 4/14 (28.6%)
    Increased creatinine 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Lymphocyte count decreased 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 3/14 (21.4%)
    Lymphocyte count increased 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Neutrophil count decreased 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 4/14 (28.6%)
    Platelet count decreased 2/3 (66.7%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 2/6 (33.3%) 9/14 (64.3%)
    White blood cell decreased 2/3 (66.7%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 2/6 (33.3%) 11/14 (78.6%)
    Metabolism and nutrition disorders
    Anorexia 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 1/6 (16.7%) 0/14 (0%)
    Dehydration 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Hypercalcemia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Hyperglycemia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Hyperkalemia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Hypernatremia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypoalbuminemia 0/3 (0%) 3/3 (100%) 0/3 (0%) 1/6 (16.7%) 2/6 (33.3%) 3/14 (21.4%)
    Hypocalcemia 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 2/6 (33.3%) 5/6 (83.3%) 4/14 (28.6%)
    Hypoglycemia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Hypokalemia 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 2/6 (33.3%) 6/14 (42.9%)
    Hypomagnesemia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/6 (50%) 4/14 (28.6%)
    Hyponatremia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/6 (33.3%) 3/14 (21.4%)
    Hypophosphatemia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Tumor lysis syndrome 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Back pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/14 (0%)
    Bone pain 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 2/6 (33.3%) 3/6 (50%) 0/14 (0%)
    Generalized muscle weakness 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Myalgia 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/14 (0%)
    Neck pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Submandibular mass 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Inclusion cyst - mid thoracic back 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Nervous system disorders
    Dizziness 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 2/6 (33.3%) 1/14 (7.1%)
    Dysesthesia 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Dysphasia 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/14 (0%)
    Headache 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 4/6 (66.7%) 3/6 (50%) 3/14 (21.4%)
    Hypersomnia 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Paresthesia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 1/6 (16.7%) 1/14 (7.1%)
    Peripheral sensory neuropathy 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Sinus pain 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Stroke 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Subdural hematoma 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Syncope 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Tremor 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Intracranial hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Psychiatric disorders
    Anxiety 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Delirium 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Depression 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hallucinations 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Insomnia 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 1/6 (16.7%) 3/14 (21.4%)
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 1/14 (7.1%)
    Dysuria 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Enlarged bladder 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Hematuria 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/14 (14.3%)
    Proteinuria 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 3/14 (21.4%)
    Urinary retention 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Urinary urgency 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Atelectasis 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Cough 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/6 (16.7%) 1/14 (7.1%)
    Dyspnea 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 3/6 (50%) 1/6 (16.7%) 0/14 (0%)
    Epistaxis 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Hypoxia 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Laryngeal hemorrhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Nasal congestion 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/14 (0%)
    Pleural effusion 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Pleural hemmorhage 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Pneumonitis 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 4/14 (28.6%)
    Productive cough 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Pulmonary edema 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/14 (7.1%)
    Respiratory failure 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Wheezing 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Papulopustular rash 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Pruritus 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 0/6 (0%) 0/14 (0%)
    Rash maculo-papular 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/6 (33.3%) 2/14 (14.3%)
    Scalp pain 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/14 (0%)
    Skin ulceration 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 1/14 (7.1%)
    Vascular disorders
    Hot flashes 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypertension 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 1/14 (7.1%)
    Hypotension 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/6 (16.7%) 6/14 (42.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Geoffrey Uy, M.D.
    Organization Washington University School of Medicine
    Phone 314-454-8304
    Email guy@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00906945
    Other Study ID Numbers:
    • 10-0910 / 201106039
    First Posted:
    May 21, 2009
    Last Update Posted:
    Apr 4, 2017
    Last Verified:
    Feb 1, 2017