Study of IMC-EB10 in Participant With Leukemia
- Conditions
- Myeloid Leukemia
- Interventions
- Biological: IMC-EB10
- Registration Number
- NCT00887926
- Lead Sponsor
- Eli Lilly and Company
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
- 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
- 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IMC-EB10 5 milligrams/kilogram (mg/kg) IMC-EB10 All participants will receive intravenous infusions of IMC-EB10, with the dose depending on which cohort they are enrolled into.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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) 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) 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
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.
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) 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.
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.
Trial Locations
- Locations (1)
ImClone Investigational Site
🇺🇸Houston, Texas, United States