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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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
ImClone Investigational Site
Columbus, Ohio, United States
ImClone Investigational Site
Houston, Texas, United States
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).
Time frame: Cycle 1 (28-day cycle)
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)
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 8 weeks and 30-day post-treatment follow-up
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.
Time frame: Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles)
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.
Time frame: 4 weeks
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.
Time frame: Week 4 and Week 8