Study of IMC-EB10 in Participant With Leukemia

NCT00887926 | Terminated Phase 1 Results

• 3 other identifiers: 13959CP17-0801I5C-IE-JEBA
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Myeloid Leukemia

Keywords

AML; Leukemia; Acute Myeloid Leukemia; Antibodies, Monoclonal

Outcome Measures

Primary Outcomes (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).

  Cycle 1 (28-day cycle)

Secondary Outcomes (7)

• 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)

• 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

• Number of Participants With Anti-IMC-EB10 Antibodies

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

Study Arms (1)

IMC-EB10 5 milligrams/kilogram (mg/kg)

EXPERIMENTAL

All participants will receive intravenous infusions of IMC-EB10, with the dose depending on which cohort they are enrolled into.

Biological: IMC-EB10

Interventions

IMC-EB10 BIOLOGICAL

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

Also known as: LY3012218

IMC-EB10 5 milligrams/kilogram (mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

ImClone Investigational Site

Columbus, Ohio, 43210, United States

Location

ImClone Investigational Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute

Interventions

IMC-EB10

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• E-mail: ClinicalTrials@ ImClone.com

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 24, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: December 22, 2022
• Results First Posted: September 11, 2019

Record last verified: 2022-12

Locations

US (2)