Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

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

IMC-EB10

E-mail: ClinicalTrials@ ImClone.com

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.

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 of IMC-EB10 in Participant With Leukemia

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

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).

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

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.

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.

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

Eli Lilly and Company

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.

Cohort 1 - 5mg/kg IMC-EB10

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.

Cohort 2 - 10 mg/kg IMC-EB10

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.

Cohort 3 - 20 mg/kg IMC-EB10

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.

Cohort 4 - 30 mg/kg IMC-EB10

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

All enrolled participants who received at least 1 dose of study drug.

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

Chief Medical Officer

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).

IMC-EB10 5 to 30 mg/kg

All participants who received at least 1 dose of study drug.

Maximum Tolerate Dose (MTD) of IMC-EB10

Week 1

Week 3

All randomized participants with Cmax results.

Pharmacokinetic (PK): Maximum Concentration (Cmax)

All randomized participants with AUC(0-last) results.

PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)]

All randomized participants with AUCtau results.

PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours

SAEs

Other Non-Serious AEs

Cohort 1 5mg/kg IMC-EB10

All randomized participants who received at least 1 dose of study drug.

Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10)

Zero participants were analyzed. The study was discontinued early due to lack of efficacy and no data was collected.

Number of Participants With Anti-IMC-EB10 Antibodies

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.

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

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.

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

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.

Spots Global Cancer Trial Database for Study of IMC-EB10 in Participant With Leukemia

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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