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Study of IMC-EB10 in Participant With Leukemia

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT00887926
Collaborator
(none)
26
Enrollment
2
Locations
1
Arm
14
Duration (Months)
13
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if IMC-EB10 is safe for participants with leukemia, and also to determine the best dose of IMC-EB10 to give to participants.

Condition or Disease Intervention/Treatment Phase
  • Biological: IMC-EB10
 Phase 1

Detailed Description

The purpose of this study is to define the maximum tolerated dose (MTD) and the pharmacokinetic (PK) profile of the anti-FMS-like tyrosine kinase 3 (FLT3) monoclonal antibody IMC-EB10, administered weekly in participant with acute lymphoblastic leukemia (AML) who have failed to achieve complete remission to a standard induction regimen, relapsed after response to previous antileukemia therapy, or are not eligible for potentially curative or approved salvage options.

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Dose Escalation, Phase I Study of IMC-EB10 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Aug 1, 2010
Actual Study Completion Date :
Aug 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: IMC-EB10 5 milligrams/kilogram (mg/kg)

All participants will receive intravenous infusions of IMC-EB10, with the dose depending on which cohort they are enrolled into.

Biological: IMC-EB10
Cohort 1 will receive IMC-EB10 intravenously for 3 weekly infusions, followed by a 1-week observation period. The starting dose in Cohort 1 will be 5 mg/kg. After all participants in Cohort 1 complete the first cycle of therapy, dose escalation for subsequent cohorts will proceed as follows: Cohort 2 - 10 mg/kg, Cohort 3 - 20 mg/kg, Cohort 4 - 30 mg/kg. Participants who experience a dose-limiting toxicity (DLT) will not receive further IMC-EB10 treatment, but will continue to be followed on the protocol. Participants may continue to receive IMC-EB10 therapy, in the absence of treatment failure, treatment intolerance, or other withdrawal criteria for additional 28-day cycles at the same dose that they initially received. Dosing for Cycle 2 and beyond will be administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle
Other Names:
  • LY3012218

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerate Dose (MTD) of IMC-EB10 [Cycle 1 (28-day cycle)]

      MTD is defined as the dose preceding the dose level at which 2 participants experienced a dose limiting toxicity (DLT) during Cycle 1. DLT is defined using National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v 3.0): (1) any Grade 3 or 4 toxicity that is clearly not attributable to leukemia [for example (e.g.) a type of end-organ failure that is infrequently encountered in acute myeloid leukemia (AML)] and is possibly, probably, or definitely attributable to IMC-EB10 in the judgment of the investigator; and (2) any Grade 3 or 4 toxicity that is clearly not attributable to a co-medication (e.g., prolonged neutropenia that is not attributable to hydroxyurea).

    Secondary Outcome Measures

    1. Pharmacokinetic (PK): Maximum Concentration (Cmax) [Cycle 1 Week 1: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 96, and 168 h after infusion ends, and Cycle 1 Week 3: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycles)]

    2. PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)] [Cycle 1 Week 1: predose, immediately after infusion, and at 1.5, 2, 4, 8, 24, 96 and 168 h after infusion ends (28-day cycle)]

    3. PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours [Cycle 1 Week 3: predose, immediately after infusion and at 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycle)]

    4. Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10) [8 weeks and 30-day post-treatment follow-up]

      Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module

    5. Number of Participants With Anti-IMC-EB10 Antibodies [Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles)]

      A participant is considered positive for antibodies against IMC-EB10 if their blood sample exhibited a post-treatment antibody level that exceeds the positive upper cut point determined from the anti-IMC-EB10 level in healthy untreated individuals. A participant was considered to have an anti-IMC-EB10 response if there are 2 consecutive positive samples or if the final sample tested is positive.

    6. Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR) [4 weeks]

      Assessment of antileukemic response was based on hematologic response criteria. PR defined as >1000/microliter (µL) neutrophils and ≥100000/µL platelets in peripheral blood; a decrease of ≥50% in the pretreatment percentage of blasts to 5% to 25% in the bone marrow aspirate or a value of ≤5% blasts if Auer rods are present. Cytogenetic CR defined as normal cytogenetic findings. Molecular CR defined as negative findings for minimal residual disease by automated quantitative Reverse-Transcription-Polymerase Chain Reaction (RT-PCR) and multidimensional flow cytometry. Morphologic CR with incomplete blood count recovery defined as ≤5% blasts (containing no Auer rods) in a bone marrow aspirate with spicules; neutrophil count < 1000/µL or platelets <100000/mL in peripheral blood or no extramedullary leukemia present.

    7. Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response [Week 4 and Week 8]

      FLT3 response to IMC-EB10 is defined as wild type, internal tandem duplications (ITD) mutations and other mutations.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. The participant has acute myeloid leukemia in the bone marrow or blood that has relapsed with or without a prior complete remission

    2. The participant is not regarded to be a candidate for a potentially curative, higher priority treatment for acute myeloid leukemia

    3. The participant has resolution of all clinically significant toxic effects of any prior antitumor therapy and any other study-specific clinical or laboratory parameter specified in the entry criteria

    4. The participant has not had major surgery, an open biopsy, a significant injury, and/or prior antitumor therapy (except antileukemia therapy) within 21 days prior to the first infusion of IMC-EB10

    5. The participant has an Eastern Cooperative Oncology Group (ECOG)performance status of 0, 1, or 2 at study entry.

    6. The participant is age 18 years or older

    7. The participant has a life expectancy of >3 months

    8. The participant has adequate liver and kidney function, as defined in the entry criteria

    9. The participant is using an effective contraception (per the institutional standard), if procreative potential exists

    10. The participant is able to give written informed consent

    11. The participant is willing and able to comply with study procedures, scheduled visits, and treatment plans

    Exclusion Criteria:

    1. The participant has had prior allogenic or autologous stem cell transplant within <3 months of the first infusion of IMC-EB10

    2. The participant has had an organ transplant (nonhematologic) within 3 years of study entry

    3. The participant has active central nervous system leukemia

    4. The participant has extramedullary disease without peripheral/and or bone marrow involvement

    5. The participant is disease-free from a previous or concurrent malignancy for a period ≤ 1 year. A participant who has basal cell carcinoma or carcinoma in situ of the cervix will not be excluded from the study

    6. The participant is currently receiving antileukemia therapy. Concurrent treatment with hydroxyurea is permitted

    7. The participant has uncontrolled intercurrent illness as specified in the study entry criteria

    8. The participant is receiving chronic steroid or other immunosuppressive medications. Occasional use of steroid-containing medications for, for example (e.g.), asthma exacerbation or for skin lesions, is permitted

    9. The participant is receiving full-dose heparin (including low molecular weight heparin) or warfarin. [The participant is permitted to use low-dose warfarin to maintain patency of preexisting, permanent, indwelling intravenous (I.V.) catheters.]

    10. The participant is pregnant (confirmed by urine or serum pregnancy test) or breast feeding

    11. The participant has received treatment with monoclonal antibodies within 6 weeks prior to first infusion of IMC-EB10

    12. The participant has a history of clinically significant allergic reactions to monoclonal antibodies or other therapeutic proteins

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ImClone Investigational Site Columbus Ohio United States 43210
    2 ImClone Investigational Site Houston Texas United States 77030

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00887926
    Other Study ID Numbers:
    • 13959
    • CP17-0801
    • I5C-IE-JEBA
    First Posted:
    Apr 24, 2009
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Feb 1, 2012
    Keywords provided by Eli Lilly and Company
    AML
    Leukemia
    Acute Myeloid Leukemia
    Antibodies, Monoclonal
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participant Flow is reporting enrolled participants who discontinued from the study. Participants who died or had progressive disease (PD) were considered to have completed the study.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 (LY3012218) Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 milligrams/kilogram (mg/kg) administered intravenously (IV) on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Period Title: Overall Study
    STARTED 3 14 3 5
    Received at Least 1 Dose of Study Drug 3 13 3 5
    COMPLETED 3 13 3 5
    NOT COMPLETED 0 1 0 0

    Baseline Characteristics

    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10 Total
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. Total of all reporting groups
    Overall Participants 3 13 3 5 24
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    67.7
    (5.97)
    63.9
    (18.52)
    74.8
    (4.45)
    60.3
    (16.91)
    65.0
    (15.89)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    8
    61.5%
    1
    33.3%
    1
    20%
    10
    41.7%
    Male
    3
    100%
    5
    38.5%
    2
    66.7%
    4
    80%
    14
    58.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    7.7%
    0
    0%
    0
    0%
    1
    4.2%
    Asian
    0
    0%
    2
    15.4%
    0
    0%
    1
    20%
    3
    12.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    3
    100%
    10
    76.9%
    3
    100%
    3
    60%
    19
    79.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    1
    4.2%
    Region of Enrollment (Count of Participants)
    United States
    3
    100%
    13
    100%
    3
    100%
    5
    100%
    24
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerate Dose (MTD) of IMC-EB10
    Description MTD is defined as the dose preceding the dose level at which 2 participants experienced a dose limiting toxicity (DLT) during Cycle 1. DLT is defined using National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v 3.0): (1) any Grade 3 or 4 toxicity that is clearly not attributable to leukemia [for example (e.g.) a type of end-organ failure that is infrequently encountered in acute myeloid leukemia (AML)] and is possibly, probably, or definitely attributable to IMC-EB10 in the judgment of the investigator; and (2) any Grade 3 or 4 toxicity that is clearly not attributable to a co-medication (e.g., prolonged neutropenia that is not attributable to hydroxyurea).
    Time Frame Cycle 1 (28-day cycle)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug.
    Arm/Group Title IMC-EB10 5 to 30 mg/kg
    Arm/Group Description Participants received either 5, 10, 20 or 30 mg/kg of IMC-EB10 IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle).
    Measure Participants 24
    Number [mg/kg]
    NA
    2. Secondary Outcome
    Title Pharmacokinetic (PK): Maximum Concentration (Cmax)
    Description
    Time Frame Cycle 1 Week 1: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 96, and 168 h after infusion ends, and Cycle 1 Week 3: predose, immediately after infusion, and 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycles)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with Cmax results.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 3 11 3 4
    Week 1
    129
    (25)
    254
    (35)
    896
    (30)
    927
    (38)
    Week 3
    119
    (24)
    781
    (66)
    1520
    (9)
    1770
    (74)
    3. Secondary Outcome
    Title PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)]
    Description
    Time Frame Cycle 1 Week 1: predose, immediately after infusion, and at 1.5, 2, 4, 8, 24, 96 and 168 h after infusion ends (28-day cycle)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with AUC(0-last) results.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 3 10 3 3
    Geometric Mean (Geometric Coefficient of Variation) [micrograms * hours/milliliter (µg*h/mL)]
    9090
    (39)
    23300
    (27)
    71800
    (40)
    77200
    (69)
    4. Secondary Outcome
    Title PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours
    Description
    Time Frame Cycle 1 Week 3: predose, immediately after infusion and at 1.5, 2, 4, 8, 24, 48, 96,168, 240 and 336 h after infusion ends (28-day cycle)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with AUCtau results.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 2 5 3 2
    Geometric Mean (Geometric Coefficient of Variation) [µg*h/mL]
    NA
    (NA)
    72500
    (41)
    108000
    (39)
    NA
    (NA)
    5. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10)
    Description Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module
    Time Frame 8 weeks and 30-day post-treatment follow-up

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Cohort 1 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 3 13 3 5
    SAEs
    1
    33.3%
    7
    53.8%
    1
    33.3%
    3
    60%
    Other Non-Serious AEs
    3
    100%
    11
    84.6%
    3
    100%
    5
    100%
    6. Secondary Outcome
    Title Number of Participants With Anti-IMC-EB10 Antibodies
    Description A participant is considered positive for antibodies against IMC-EB10 if their blood sample exhibited a post-treatment antibody level that exceeds the positive upper cut point determined from the anti-IMC-EB10 level in healthy untreated individuals. A participant was considered to have an anti-IMC-EB10 response if there are 2 consecutive positive samples or if the final sample tested is positive.
    Time Frame Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles)

    Outcome Measure Data

    Analysis Population Description
    Zero participants were analyzed. The study was discontinued early due to lack of efficacy and no data was collected.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 0 0 0 0
    7. Secondary Outcome
    Title Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR)
    Description Assessment of antileukemic response was based on hematologic response criteria. PR defined as >1000/microliter (µL) neutrophils and ≥100000/µL platelets in peripheral blood; a decrease of ≥50% in the pretreatment percentage of blasts to 5% to 25% in the bone marrow aspirate or a value of ≤5% blasts if Auer rods are present. Cytogenetic CR defined as normal cytogenetic findings. Molecular CR defined as negative findings for minimal residual disease by automated quantitative Reverse-Transcription-Polymerase Chain Reaction (RT-PCR) and multidimensional flow cytometry. Morphologic CR with incomplete blood count recovery defined as ≤5% blasts (containing no Auer rods) in a bone marrow aspirate with spicules; neutrophil count < 1000/µL or platelets <100000/mL in peripheral blood or no extramedullary leukemia present.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug.No anti-leukemic responses were observed as there were no responders due to high rate of treatment failures and were not evaluable.
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 3 13 3 5
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response
    Description FLT3 response to IMC-EB10 is defined as wild type, internal tandem duplications (ITD) mutations and other mutations.
    Time Frame Week 4 and Week 8

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug. No tyrosine kinase responses were observed as there were no responders due to high rate of treatment failures and were not evaluable.
    Arm/Group Title Cohort 1 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    Measure Participants 3 13 3 5
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Arm/Group Description IMC-EB10: 5 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 10 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 20 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles. IMC-EB10: 30 mg/kg administered IV on Days 1, 8, and 15 of Cycle 1 (28-day cycle) and Days 1, 8, 15, and 22 of subsequent 28-day cycles.
    All Cause Mortality
    Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 7/13 (53.8%) 1/3 (33.3%) 3/5 (60%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Neutropenia 1/3 (33.3%) 1 1/13 (7.7%) 1 1/3 (33.3%) 1 0/5 (0%) 0
    Cardiac disorders
    Arrhythmia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    General disorders
    Disease progression 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Infections and infestations
    Herpes zoster disseminated 0/3 (0%) 0 0/13 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0
    Pneumonia 1/3 (33.3%) 1 5/13 (38.5%) 5 0/3 (0%) 0 0/5 (0%) 0
    Sepsis 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Aspartate aminotransferase increased 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Nervous system disorders
    Cerebral haemorrhage 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Renal and urinary disorders
    Renal failure acute 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort 1 - 5mg/kg IMC-EB10 Cohort 2 - 10 mg/kg IMC-EB10 Cohort 3 - 20 mg/kg IMC-EB10 Cohort 4 - 30 mg/kg IMC-EB10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 11/13 (84.6%) 3/3 (100%) 5/5 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 0 6/13 (46.2%) 7 1/3 (33.3%) 1 2/5 (40%) 3
    Coagulopathy 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Febrile neutropenia 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 1/5 (20%) 1
    Leukocytosis 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Leukopenia 0/3 (0%) 0 1/13 (7.7%) 3 1/3 (33.3%) 1 1/5 (20%) 1
    Lymphopenia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Neutropenia 0/3 (0%) 0 0/13 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0
    Thrombocytopenia 0/3 (0%) 0 2/13 (15.4%) 3 1/3 (33.3%) 1 0/5 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Atrial fibrillation 2/3 (66.7%) 2 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Atrial flutter 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Bradycardia 1/3 (33.3%) 1 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Cardiac failure 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Cyanosis 0/3 (0%) 0 1/13 (7.7%) 2 0/3 (0%) 0 0/5 (0%) 0
    Tachycardia 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 1/5 (20%) 1
    Eye disorders
    Conjunctival pallor 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Vision blurred 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 1/3 (33.3%) 1 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Ascites 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Constipation 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Diarrhoea 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Gingival bleeding 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Haemorrhoids 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Mouth ulceration 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Nausea 0/3 (0%) 0 4/13 (30.8%) 4 0/3 (0%) 0 1/5 (20%) 1
    Oral pain 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Pancreatitis acute 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Proctalgia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Tongue ulceration 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Vomiting 0/3 (0%) 0 3/13 (23.1%) 3 0/3 (0%) 0 0/5 (0%) 0
    General disorders
    Asthenia 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Chills 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Fatigue 1/3 (33.3%) 1 4/13 (30.8%) 4 0/3 (0%) 0 0/5 (0%) 0
    Generalised oedema 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Mucosal inflammation 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Multi-organ failure 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Oedema peripheral 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Pain 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Pyrexia 2/3 (66.7%) 2 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Hepatobiliary disorders
    Hepatic failure 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Hyperbilirubinaemia 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Infections and infestations
    Candidiasis 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Enterococcal bacteraemia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Septic shock 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Stenotrophomonas infection 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Urinary tract infection 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 0/13 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0
    Aspartate aminotransferase increased 0/3 (0%) 0 0/13 (0%) 0 1/3 (33.3%) 1 1/5 (20%) 1
    Blood alkaline phosphatase increased 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Cardiac murmur 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Weight decreased 1/3 (33.3%) 1 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Metabolism and nutrition disorders
    Acidosis 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Decreased appetite 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Fluid overload 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Hyperglycaemia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Hyperkalaemia 0/3 (0%) 0 1/13 (7.7%) 1 1/3 (33.3%) 1 0/5 (0%) 0
    Hypocalcaemia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Hyponatraemia 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Lactic acidosis 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Malnutrition 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Metabolic acidosis 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Gouty arthritis 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Musculoskeletal chest pain 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Musculoskeletal pain 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Myalgia 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Pain in extremity 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Nervous system disorders
    Dizziness 1/3 (33.3%) 1 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Headache 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Neuropathy peripheral 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Sinus headache 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Psychiatric disorders
    Anxiety 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Insomnia 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Renal and urinary disorders
    Anuria 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Renal failure acute 0/3 (0%) 0 3/13 (23.1%) 3 1/3 (33.3%) 1 0/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Cough 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Dyspnoea 0/3 (0%) 0 3/13 (23.1%) 3 0/3 (0%) 0 0/5 (0%) 0
    Epistaxis 1/3 (33.3%) 1 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Hypoxia 0/3 (0%) 0 1/13 (7.7%) 2 0/3 (0%) 0 0/5 (0%) 0
    Oropharyngeal pain 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Paranasal sinus hypersecretion 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Pleural effusion 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Pulmonary oedema 0/3 (0%) 0 0/13 (0%) 0 0/3 (0%) 0 1/5 (20%) 1
    Respiratory failure 0/3 (0%) 0 2/13 (15.4%) 2 0/3 (0%) 0 0/5 (0%) 0
    Skin and subcutaneous tissue disorders
    Petechiae 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Pruritus 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Rash maculo-papular 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 1/5 (20%) 1
    Urticaria 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/3 (33.3%) 1 0/13 (0%) 0 0/3 (0%) 0 0/5 (0%) 0
    Haemodynamic instability 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0
    Hypotension 1/3 (33.3%) 1 4/13 (30.8%) 4 0/3 (0%) 0 0/5 (0%) 0
    Pallor 0/3 (0%) 0 1/13 (7.7%) 1 0/3 (0%) 0 0/5 (0%) 0

    Limitations/Caveats

    Because development of IMC-EB10 was put on hold due to lack of efficacy analyses were not carried out as planned.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00887926
    Other Study ID Numbers:
    • 13959
    • CP17-0801
    • I5C-IE-JEBA
    First Posted:
    Apr 24, 2009
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Feb 1, 2012