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Myeloid LeukemiaPhase 1NCT00887926

Study of IMC-EB10 in Participant With Leukemia

A Phase 1 study testing IMC-EB10 in people with Myeloid Leukemia, run by Eli Lilly and Company at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myeloid Leukemia
What is being tested?
IMC-EB10
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
Jun 2009to Aug 2010
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant has acute myeloid leukemia in the bone marrow or blood that has relapsed with or without a prior complete remission
  • The participant is not regarded to be a candidate for a potentially curative, higher priority treatment for acute myeloid leukemia
  • 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
  • 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
  • The participant has an Eastern Cooperative Oncology Group (ECOG)performance status of 0, 1, or 2 at study entry.
  • The participant is age 18 years or older
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  • The participant has a life expectancy of >3 months
  • The participant has adequate liver and kidney function, as defined in the entry criteria
  • The participant is using an effective contraception (per the institutional standard), if procreative potential exists
  • The participant is able to give written informed consent
  • The participant is willing and able to comply with study procedures, scheduled visits, and treatment plans

Who cannot join

  • The participant has had prior allogenic or autologous stem cell transplant within <3 months of the first infusion of IMC-EB10
  • The participant has had an organ transplant (nonhematologic) within 3 years of study entry
  • The participant has active central nervous system leukemia
  • The participant has extramedullary disease without peripheral/and or bone marrow involvement
  • 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
  • The participant is currently receiving antileukemia therapy. Concurrent treatment with hydroxyurea is permitted
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  • The participant has uncontrolled intercurrent illness as specified in the study entry criteria
  • 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
  • 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.]
  • The participant is pregnant (confirmed by urine or serum pregnancy test) or breast feeding
  • The participant has received treatment with monoclonal antibodies within 6 weeks prior to first infusion of IMC-EB10
  • The participant has a history of clinically significant allergic reactions to monoclonal antibodies or other therapeutic proteins

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • ImClone Investigational Site

    Columbus, Ohio, 43210

  • ImClone Investigational Site

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: An Open-label, Dose Escalation, Phase I Study of IMC-EB10 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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.

Read the 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.

Being tested
IMC-EB10
Keywords
AML, Leukemia, Acute Myeloid Leukemia, Antibodies, Monoclonal
Medical subject headings
Leukemia, Myeloid, Leukemia, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMC-EB10Biological

    Also called LY3012218

    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

Study groups in NCT00887926
Study groupRoleWhat they receive
IMC-EB10 5 milligrams/kilogram (mg/kg)ExperimentalAll participants will receive intravenous infusions of IMC-EB10, with the dose depending on which cohort they are enrolled into.
Receives: Biological: IMC-EB10

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerate Dose (MTD) of IMC-EB10

    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).

    Measured: Cycle 1 (28-day cycle)

Secondary outcomes (7)

  1. Pharmacokinetic (PK): Maximum Concentration (Cmax)

    Measured: 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)]

    Measured: 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

    Measured: 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)

    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

    Measured: 8 weeks and 30-day post-treatment follow-up

  5. Number of Participants With Anti-IMC-EB10 Antibodies

    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.

    Measured: Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles)

  6. Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR)

    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.

    Measured: 4 weeks

  7. Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response

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

    Measured: Week 4 and Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionAug 2010
  4. Study completionAug 2010

Why it stopped: Lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00887926
Sponsor's protocol ID
13959
Other IDs
CP17-0801, I5C-IE-JEBA
Status last verified
Dec 2022
First submitted
23 Apr 2009
Last updated
22 Dec 2022
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IMC-EB10 in people with Myeloid Leukemia, run by Eli Lilly and Company at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerate Dose (MTD) of IMC-EB10 (time frame: Cycle 1 (28-day cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00887926.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.

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