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AMD3100+MEC: AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT00512252
Collaborator
(none)
52
Enrollment
1
Location
2
Arms
35
Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

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.

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

Detailed Description

The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although a number of receptor / ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being developed clinically as a mobilization agent for hematopoietic stem cell transplantation. Preclinical data from our group has demonstrated that in murine models, plerixafor can disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II study in patients with relapsed or refractory AML in which plerixafor is administered prior to salvage chemotherapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML
Study Start Date :
Jul 1, 2007
Actual Primary Completion Date :
Jun 1, 2010
Actual Study Completion Date :
Jun 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase I Dose Escalation

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

Drug: AMD3100
Other Names:
  • Plerixafor

    • Drug: Mitoxantrone
    Other Names:
  • Novantrone

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

    • Drug: Cytarabine
    Other Names:
  • Ara-C
  • Cytosar-U
  • Tarabine PFS

    		•
    Experimental: Phase II Dose Treatment

    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)

    Drug: AMD3100
    Other Names:
  • Plerixafor

    • Drug: Mitoxantrone
    Other Names:
  • Novantrone

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

    • Drug: Cytarabine
    Other Names:
  • Ara-C
  • Cytosar-U
  • Tarabine PFS

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML [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.

    2. Phase II Only: Complete Response Rate of AMD3100 + MEC [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).

    3. Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions [42 days]

    Secondary Outcome Measures

    1. Safety and Tolerability of AMD3100 + MEC. [42 days]

      Treatment related mortality (deaths occurring during treatment)

    2. Time to Neutrophil Recovery [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.

    3. Time to Platelet Recovery [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.

    4. Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I) [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.

    5. Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I) [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.

    6. Pharmacokinetics of AMD3100 on MEC [Day 1 - Phase 2 only]

    7. Time to Progression [Every 6 months]

    8. Treatment Failure [42 days]

      Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.

    9. Overall Survival [1 year]

    10. Relapse-free Survival [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.

    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:

    2. Primary refractory disease following >= 1 rounds of induction chemotherapy

    3. First relapse or higher

    4. Age between 18 and 70 years of age

    5. 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

    6. Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study

    7. 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. Receiving any other investigational agent

    7. Colony stimulating factors filgrastim, pegfilgrastim or sargramostim within 2 weeks of study

    8. Less than 2 weeks from the completion of any previous cytotoxic chemotherapy

    9. Severe concurrent illness that would limit compliance with study requirements

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University St. Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Geoffrey L. Uy, MD, 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:
    NCT00512252
    Other Study ID Numbers:
    • 07-0227 / 201011796
    First Posted:
    Aug 7, 2007
    Last Update Posted:
    Dec 12, 2016
    Last Verified:
    Oct 1, 2016
    Keywords provided by Washington University School of Medicine
    Plerixafor
    CXCR4
    Chemosensitization
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Cytarabine
    Plerixafor
    Etoposide
    Mitoxantrone

    Study Results

    Participant Flow

    Recruitment Details Recruitment occurred from 07/12/2007 until 01/14/2010.
    Pre-assignment Detail
    Arm/Group Title Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3)
    Arm/Group Description 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 AMD3100 SQ on days 0-5 Mitoxantrone on days 1-5 Etoposide on days 1-5 Cytarabine on days 1-5 Dose Level 2 AMD3100 dose = 160 mcg/kg/d 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). The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose.
    Period Title: Overall Study
    STARTED 3 3 46
    COMPLETED 3 3 43
    NOT COMPLETED 0 0 3

    Baseline Characteristics

    Arm/Group Title Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3) Total
    Arm/Group Description 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 AMD3100 SQ on days 0-5 Mitoxantrone on days 1-5 Etoposide on days 1-5 Cytarabine on days 1-5 Dose Level 2 AMD3100 dose = 160 mcg/kg/d 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). The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose. Total of all reporting groups
    Overall Participants 3 3 46 52
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    1
    2.2%
    1
    1.9%
    Between 18 and 65 years
    3
    100%
    3
    100%
    40
    87%
    46
    88.5%
    >=65 years
    0
    0%
    0
    0%
    5
    10.9%
    5
    9.6%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    58
    24
    51
    51
    Gender (Count of Participants)
    Female
    2
    66.7%
    2
    66.7%
    26
    56.5%
    30
    57.7%
    Male
    1
    33.3%
    1
    33.3%
    20
    43.5%
    22
    42.3%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    46
    100%
    52
    100%
    Acute myeloid leukemia (AML) source (participants) [Number]
    De novo AML
    3
    100%
    2
    66.7%
    36
    78.3%
    41
    78.8%
    Therapy related
    0
    0%
    1
    33.3%
    4
    8.7%
    5
    9.6%
    Prior MDS/MPD
    0
    0%
    0
    0%
    6
    13%
    6
    11.5%
    Prior transplantation (participants) [Number]
    Autologous
    0
    0%
    0
    0%
    3
    6.5%
    3
    5.8%
    Allogeneic
    0
    0%
    0
    0%
    6
    13%
    6
    11.5%
    No prior transplant
    3
    100%
    3
    100%
    37
    80.4%
    43
    82.7%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
    0
    2
    66.7%
    2
    66.7%
    25
    54.3%
    29
    55.8%
    1
    1
    33.3%
    1
    33.3%
    10
    21.7%
    12
    23.1%
    2
    0
    0%
    0
    0%
    3
    6.5%
    3
    5.8%
    Unknown
    0
    0%
    0
    0%
    8
    17.4%
    8
    15.4%
    Treatment Indication (participants) [Number]
    First relapse, first salvage
    3
    100%
    2
    66.7%
    32
    69.6%
    37
    71.2%
    Primary refractory
    0
    0%
    1
    33.3%
    10
    21.7%
    11
    21.2%
    >=Second relapse/salvage
    0
    0%
    0
    0%
    4
    8.7%
    4
    7.7%

    Outcome Measures

    1. Primary Outcome
    Title Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
    Description 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.
    Time Frame Completion of all patients in Phase I portion (232 days)

    Outcome Measure Data

    Analysis Population Description
    The Phase I Dose Escalation portion included (3) patients enrolled in Dose Level 1 and (3) patients enrolled in Dose Level 2. The (6) patients enrolled in Dose Level 3 that determined the Phase II dose are included in the population for this outcome.
    Arm/Group Title Phase I Dose Escalation
    Arm/Group Description 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 Dose Level 3 AMD3100 dose = 240 mcg/kg/d
    Measure Participants 12
    Number [mcg/kg]
    240
    2. Primary Outcome
    Title Phase II Only: Complete Response Rate of AMD3100 + MEC
    Description 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).
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title First Relapse, First Salvage Primary Refractory >= Second Relapse/Salvage Total
    Arm/Group Description Phase II Dose Patients
    Measure Participants 32 10 4 46
    CR + CRi
    56
    1866.7%
    20
    666.7%
    25
    54.3%
    46
    88.5%
    CR only
    47
    1566.7%
    20
    666.7%
    25
    54.3%
    39
    75%
    3. Primary Outcome
    Title Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions
    Description
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    This outcome was not analyzed as data was not collected.
    Arm/Group Title Phase I Dose Escalation/Phase II Dose Treatment
    Arm/Group Description
    Measure Participants 0
    4. Secondary Outcome
    Title Safety and Tolerability of AMD3100 + MEC.
    Description Treatment related mortality (deaths occurring during treatment)
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    The 46 patients include the 6 patients treated on Dose Level 3 of the Phase I portion of the study.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 46
    Sepsis
    2
    66.7%
    Adverse transfusion reaction w/febrile neutropenia
    1
    33.3%
    5. Secondary Outcome
    Title Time to Neutrophil Recovery
    Description Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count >1,000 cells/mm^3.
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    This analysis includes patients who achieved a CR or a CRi.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 21
    Median (Full Range) [days]
    28
    6. Secondary Outcome
    Title Time to Platelet Recovery
    Description 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.
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    This analysis includes patients who achieved a CR.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 18
    Median (Full Range) [days]
    28.5
    7. Secondary Outcome
    Title Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
    Description 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.
    Time Frame Day 0

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I Dose Escalation - Dose Level 1 Phase I Dose Escalation - Dose Level 2 Phase I Dose Escalation - Dose Level 3
    Arm/Group Description 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 AMD3100 SQ on days 0-5 Mitoxantrone on days 1-5 Etoposide on days 1-5 Cytarabine on days 1-5 Dose Level 2 AMD3100 dose = 160 mcg/kg/d AMD3100 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
    Measure Participants 3 3 6
    Total leukocytes at 0 hours
    2.5
    4.7
    3.5
    Total leukocytes at 1 hour
    4.3
    7.0
    6.4
    Total leukocytes at 2 hours
    4
    8.5
    7.5
    Total leukocytes at 4 hours
    4.7
    9.4
    8.3
    Total leukocytes at 6 hours
    4.8
    11.3
    9.5
    Total leukocytes at 8 hours
    4.5
    12.0
    8.9
    Total leukocytes at 12 hours
    5.1
    12.1
    7.8
    Total leukocytes at 24 hours
    4.3
    7.9
    5.8
    8. Secondary Outcome
    Title Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
    Description 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.
    Time Frame Day 0

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I Dose Escalation - Dose Level 1 Phase I Dose Escalation - Dose Level 2 Phase I Dose Escalation - Dose Level 3
    Arm/Group Description 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 AMD3100 SQ on days 0-5 Mitoxantrone on days 1-5 Etoposide on days 1-5 Cytarabine on days 1-5 Dose Level 2 AMD3100 dose = 160 mcg/kg/d AMD3100 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
    Measure Participants 3 3 6
    AML blasts at 0 hours
    46.0
    4.0
    43.5
    AML blasts at 1 hour
    26.0
    9.0
    30.5
    AML blasts at 2 hours
    26.0
    37.5
    32.5
    AML blasts at 4 hours
    37.0
    16.0
    30.0
    AML blasts at 6 hours
    31.0
    14.0
    27.0
    AML blasts at 8 hours
    32.0
    19.0
    26.0
    AML blasts at 12 hours
    27.0
    45.0
    35.0
    AML blasts at 24 hours
    35.0
    23
    55
    9. Secondary Outcome
    Title Pharmacokinetics of AMD3100 on MEC
    Description
    Time Frame Day 1 - Phase 2 only

    Outcome Measure Data

    Analysis Population Description
    This was not performed.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 0
    10. Secondary Outcome
    Title Time to Progression
    Description
    Time Frame Every 6 months

    Outcome Measure Data

    Analysis Population Description
    This outcome was not analyzed instead "reason for treatment failure" was analyzed as it provided better information on why the treatment did not work.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 0
    11. Secondary Outcome
    Title Treatment Failure
    Description Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.
    Time Frame 42 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title First Relapse, First Salvage Primary Refractory >= Second Relapse/Salvage Total
    Arm/Group Description Phase II Dose Patients
    Measure Participants 14 8 3 25
    Persistent leukemia
    12
    400%
    6
    200%
    3
    6.5%
    21
    40.4%
    Death during aplasia
    1
    33.3%
    2
    66.7%
    0
    0%
    3
    5.8%
    Unknown
    1
    33.3%
    0
    0%
    0
    0%
    1
    1.9%
    12. Secondary Outcome
    Title Overall Survival
    Description
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 46
    Number [percentage of participants]
    37
    1233.3%
    13. Secondary Outcome
    Title Relapse-free Survival
    Description 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.
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    This excludes the 25 participants who had treatment failure.
    Arm/Group Title Phase II Dose Treatment
    Arm/Group Description 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)
    Measure Participants 21
    Number [percentage of participants]
    42.9
    1430%

    Adverse Events

    Time Frame Adverse event assessment was collected from start of treatment for 42 days
    Adverse Event Reporting Description The adverse events are not split into Phase I Dose Escalation portion and the Phase II Dose Treatment portion instead all events are reported as a whole.
    Arm/Group Title Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3)
    Arm/Group Description 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 AMD3100 SQ on days 0-5 Mitoxantrone on days 1-5 Etoposide on days 1-5 Cytarabine on days 1-5 Dose Level 2 AMD3100 dose = 160 mcg/kg/d 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). The 6 participants that were enrolled in Dose Level 3 in the Phase I portion of the study were carried over to the Phase II analysis. 40 additional patients were enrolled in the Phase II portion of the study using the Dose Level 3 dose.
    All Cause Mortality
    Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Cardiac disorders
    Hypotension 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Immune system disorders
    Allergic reaction - platelet transfusion 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Infections and infestations
    Infection-other (gram negative sepsis) 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Other (Not Including Serious) Adverse Events
    Phase I Dose Escalation (Dose Level 1) Phase I Dose Escalation (Dose Level 2) Phase II Dose Treatment (Dose Level 3)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 46/46 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 3/3 (100%) 3/3 (100%) 31/46 (67.4%)
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Bradycardia 0/3 (0%) 2/3 (66.7%) 8/46 (17.4%)
    Chest pain 1/3 (33.3%) 0/3 (0%) 4/46 (8.7%)
    Hypertension 0/3 (0%) 1/3 (33.3%) 11/46 (23.9%)
    Hypotension 2/3 (66.7%) 0/3 (0%) 10/46 (21.7%)
    Palpitations 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Supraventricular tachycardia 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Tachycardia 1/3 (33.3%) 2/3 (66.7%) 29/46 (63%)
    Vasovagal episode 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Ear and labyrinth disorders
    Ear pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right ear pain 0/3 (0%) 2/3 (66.7%) 1/46 (2.2%)
    Tinnitus 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Eye disorders
    Blurred vison 1/3 (33.3%) 0/3 (0%) 5/46 (10.9%)
    Hemorrhage - eye 1/3 (33.3%) 0/3 (0%) 2/46 (4.3%)
    Vision - floaters 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Visual changes 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Gastrointestinal disorders
    Abdominal cramping 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Abdominal pain 0/3 (0%) 2/3 (66.7%) 10/46 (21.7%)
    Colitis 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Constipation 0/3 (0%) 2/3 (66.7%) 10/46 (21.7%)
    Diarrhea 2/3 (66.7%) 2/3 (66.7%) 26/46 (56.5%)
    Distension 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Dysphagia 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Epigastric pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Esophagus pain 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Heartburn 1/3 (33.3%) 1/3 (33.3%) 3/46 (6.5%)
    Hematemesis 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Hemorrhoidal pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Hemorrhoids 1/3 (33.3%) 1/3 (33.3%) 1/46 (2.2%)
    Indigestion 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Left lower abdominal pain 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Mucositis (oral and stomach) 1/3 (33.3%) 2/3 (66.7%) 33/46 (71.7%)
    Nausea 2/3 (66.7%) 3/3 (100%) 33/46 (71.7%)
    Perianal pain 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Right upper quadrant pain 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Taste alteration 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Vomiting 2/3 (66.7%) 3/3 (100%) 17/46 (37%)
    Weight loss 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    General disorders
    Bilateral extremity echymosis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Bilateral extremity petichiae 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Chills 0/3 (0%) 1/3 (33.3%) 6/46 (13%)
    Diaphoresis 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Edema face 0/3 (0%) 0/3 (0%) 7/46 (15.2%)
    Edema limbs 1/3 (33.3%) 1/3 (33.3%) 17/46 (37%)
    Edema trunk 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Fatigue 0/3 (0%) 2/3 (66.7%) 14/46 (30.4%)
    Fever 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Generalized edema 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Generalized pain 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Hematoma 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Hypothermia 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Injection site reaction 2/3 (66.7%) 0/3 (0%) 7/46 (15.2%)
    Lip swelling 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Petichiae 0/3 (0%) 0/3 (0%) 6/46 (13%)
    Tooth pain 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Weakness 0/3 (0%) 0/3 (0%) 0/46 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Hepatomegaly 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Jaundice - right eye 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Immune system disorders
    Allergic reaction - NOS 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Allergic reaction - general itching during transfusion 1/3 (33.3%) 1/3 (33.3%) 0/46 (0%)
    Allergic reaction - platelet transfusion 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Infections and infestations
    Cellulitis 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Colitis, infectious - clostridium difficile 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Infection, gram positive cocci 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Liver abcess 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Nasal/paranasal reactions - sinusitis 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Opportunistic infection (pneumonia NOS) 0/3 (0%) 1/3 (33.3%) 2/46 (4.3%)
    Opportunistic infection - urinary tract 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Opportunistic infection, nasal 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Perirectal abscess 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Infection - gram negative sepsis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Infection - gram negative bacilli 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Injury, poisoning and procedural complications
    Bruising 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Incisional pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Injection site pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Lower back wound pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Pilonidal cyst 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Wound - coccyx 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Investigations
    ALT 1/3 (33.3%) 0/3 (0%) 14/46 (30.4%)
    AST 0/3 (0%) 1/3 (33.3%) 11/46 (23.9%)
    Alkaline phosphatase 0/3 (0%) 0/3 (0%) 20/46 (43.5%)
    Hemoglobin 3/3 (100%) 2/3 (66.7%) 17/46 (37%)
    Hyperbilirubinemia 0/3 (0%) 0/3 (0%) 7/46 (15.2%)
    Hypernatremia 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Hypoalbuminemia 2/3 (66.7%) 3/3 (100%) 17/46 (37%)
    Hypocalcemia 3/3 (100%) 1/3 (33.3%) 20/46 (43.5%)
    Hypokalemia 2/3 (66.7%) 1/3 (33.3%) 11/46 (23.9%)
    Hyponatremia 3/3 (100%) 1/3 (33.3%) 7/46 (15.2%)
    Hypophosphatemia 2/3 (66.7%) 1/3 (33.3%) 6/46 (13%)
    Leukocytes 3/3 (100%) 3/3 (100%) 38/46 (82.6%)
    Lymphopenia 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Neutrophils 3/3 (100%) 1/3 (33.3%) 21/46 (45.7%)
    Platelets 1/3 (33.3%) 2/3 (66.7%) 23/46 (50%)
    Metabolism and nutrition disorders
    Anorexia 1/3 (33.3%) 2/3 (66.7%) 25/46 (54.3%)
    Hyperkalemia 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Hyperuricemia 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/3 (0%) 2/3 (66.7%) 0/46 (0%)
    Back pain 2/3 (66.7%) 1/3 (33.3%) 8/46 (17.4%)
    Bone marrow biopsy site pain 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Coccyx pain 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Extremity pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Facial pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Flank pain 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Generalized bone pain 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Generalized joint pain 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Hip pain 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Jaw pain 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Left arm pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Left elbow pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Leg pain 0/3 (0%) 1/3 (33.3%) 2/46 (4.3%)
    Lower extremity pain 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Mouth pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Mouth pain - right side 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Muscle weakness 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Muscle weakness - generalized 1/3 (33.3%) 0/3 (0%) 24/46 (52.2%)
    Neck pain 2/3 (66.7%) 0/3 (0%) 3/46 (6.5%)
    Rib pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right arm pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right forearm pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right head and neck pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right hip pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right jaw pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Right side pain 0/3 (0%) 1/3 (33.3%) 1/46 (2.2%)
    Shoulder pain 1/3 (33.3%) 0/3 (0%) 3/46 (6.5%)
    Nervous system disorders
    Cognitive disturbance - lethargy 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Dizziness 0/3 (0%) 0/3 (0%) 5/46 (10.9%)
    Headache 2/3 (66.7%) 3/3 (100%) 19/46 (41.3%)
    Neuropathy (not specified) 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - bilateral feet 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Neuropathy - bilateral hands 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - face 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - left eye droop 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - left hand 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - right ankle 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Neuropathy - toes 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Restless leg syndrome 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Pregnancy, puerperium and perinatal conditions
    Red and swollen left labia 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Vaginal bleeding 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Psychiatric disorders
    Agitation 2/3 (66.7%) 0/3 (0%) 2/46 (4.3%)
    Anxiety 2/3 (66.7%) 3/3 (100%) 11/46 (23.9%)
    Claustrophobia 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Confusion 0/3 (0%) 0/3 (0%) 5/46 (10.9%)
    Depression 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Insomnia 0/3 (0%) 1/3 (33.3%) 14/46 (30.4%)
    Mood alteration (not specified) 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Renal and urinary disorders
    Bladder spasms 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Catheter site insertion pain 1/3 (33.3%) 1/3 (33.3%) 3/46 (6.5%)
    Dysuria 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Incontinence 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Incontinence - secondary to urinary urgency 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Renal failure 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Urinary frequency 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Urinary hesitancy 1/3 (33.3%) 0/3 (0%) 1/46 (2.2%)
    Urinary retention 1/3 (33.3%) 0/3 (0%) 2/46 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Cough 1/3 (33.3%) 1/3 (33.3%) 13/46 (28.3%)
    Dyspnea 0/3 (0%) 1/3 (33.3%) 10/46 (21.7%)
    Hemorrhage - nose 1/3 (33.3%) 0/3 (0%) 4/46 (8.7%)
    Hiccups 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Hypoxia 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Pain upon inspiration 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Pleural effusion 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Pulmonary edema 0/3 (0%) 1/3 (33.3%) 0/46 (0%)
    Sinus pain 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Sore throat 0/3 (0%) 0/3 (0%) 2/46 (4.3%)
    Tachypnea 0/3 (0%) 0/3 (0%) 4/46 (8.7%)
    Throat pain 1/3 (33.3%) 0/3 (0%) 6/46 (13%)
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Alopecia 1/3 (33.3%) 0/3 (0%) 0/46 (0%)
    Bumps on legs and arms 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Erythema 0/3 (0%) 0/3 (0%) 1/46 (2.2%)
    Itching (pruritus) 2/3 (66.7%) 0/3 (0%) 10/46 (21.7%)
    Rash 2/3 (66.7%) 3/3 (100%) 10/46 (21.7%)
    Ulceration 0/3 (0%) 0/3 (0%) 3/46 (6.5%)
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0/3 (0%) 1/46 (2.2%)

    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 L. Uy, M.D.
    Organization Washington University School of Medicine
    Phone 314-454-8304
    Email guy@dom.wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00512252
    Other Study ID Numbers:
    • 07-0227 / 201011796
    First Posted:
    Aug 7, 2007
    Last Update Posted:
    Dec 12, 2016
    Last Verified:
    Oct 1, 2016