Study of IMC-EB10 in Participant With Leukemia
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|ClinicalTrials.gov Identifier: NCT00887926|
Recruitment Status : Terminated (Lack of efficacy)
First Posted : April 24, 2009
Results First Posted : September 11, 2019
Last Update Posted : September 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Myeloid Leukemia||Biological: IMC-EB10||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||June 2009|
|Actual Primary Completion Date :||August 2010|
|Actual Study Completion Date :||August 2010|
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.
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 Name: LY3012218
- Maximum Tolerate Dose (MTD) of IMC-EB10 [ Time Frame: 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).
- Pharmacokinetic (PK): Maximum Concentration (Cmax) [ 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) ]
- PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)] [ 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) ]
- PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours [ 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) ]
- Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10) [ Time Frame: 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
- Number of Participants With Anti-IMC-EB10 Antibodies [ Time Frame: 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.
- Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR) [ Time Frame: 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.
- Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response [ Time Frame: Week 4 and Week 8 ]FLT3 response to IMC-EB10 is defined as wild type, internal tandem duplications (ITD) mutations and other mutations.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00887926
|United States, Ohio|
|ImClone Investigational Site|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|ImClone Investigational Site|
|Houston, Texas, United States, 77030|
|Study Director:||E-mail: ClinicalTrials@ ImClone.com||Eli Lilly and Company|