Clinical trial NCT00887926: Study of IMC-EB10 in Participant With Leukemia
Official title: An Open-label, Dose Escalation, Phase I Study of IMC-EB10 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Myeloid Leukemia
Keywords: AML
Leukemia
Acute Myeloid Leukemia
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-04-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. The participant has acute myeloid leukemia in the bone marrow or blood that has relapsed with or without a prior complete remission
2. The participant is not regarded to be a candidate for a potentially curative, higher priority treatment for acute myeloid leukemia
3. 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
4. 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
5. The participant has an Eastern Cooperative Oncology Group (ECOG)performance status of 0, 1, or 2 at study entry.
6. The participant is age 18 years or older
7. The participant has a life expectancy of \>3 months
8. The participant has adequate liver and kidney function, as defined in the entry criteria
9. The participant is using an effective contraception (per the institutional standard), if procreative potential exists
10. The participant is able to give written informed consent
11. The participant is willing and able to comply with study procedures, scheduled visits, and treatment plans

Exclusion Criteria:

1. The participant has had prior allogenic or autologous stem cell transplant within \<3 months of the first infusion of IMC-EB10
2. The participant has had an organ transplant (nonhematologic) within 3 years of study entry
3. The participant has active central nervous system leukemia
4. The participant has extramedullary disease without peripheral/and or bone marrow involvement
5. 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
6. The participant is currently receiving antileukemia therapy. Concurrent treatment with hydroxyurea is permitted
7. The participant has uncontrolled intercurrent illness as specified in the study entry criteria
8. 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
9. The participant is receiving full-dose heparin (including low molecular weight heparin) or warfarin. \[The participant is permitted to use low-dose warfarin to maintain patency of preexisting, permanent, indwelling intravenous (I.V.) catheters.\]
10. The participant is pregnant (confirmed by urine or serum pregnancy test) or breast feeding
11. The participant has received treatment with monoclonal antibodies within 6 weeks prior to first infusion of IMC-EB10
12. The participant has a history of clinically significant allergic reactions to monoclonal antibodies or other therapeutic proteins

Primary outcomes:
measure: Maximum Tolerate Dose (MTD) of IMC-EB10
timeFrame: Cycle 1 (28-day cycle)
Secondary outcomes:
measure: Pharmacokinetic (PK): Maximum Concentration (Cmax)
timeFrame: 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)
measure: PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Concentration [AUC(0-last)]
timeFrame: 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)
measure: PK: Area Under the Concentration Time Curve During the Dosing Interval (AUCtau) Where Tau is 168 Hours
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) (Safety Profile of IMC-EB10)
timeFrame: 8 weeks and 30-day post-treatment follow-up
measure: Number of Participants With Anti-IMC-EB10 Antibodies
timeFrame: Cycle 1, Weeks 1 and 3 and Cycle 2, Week 1: predose (28-day cycles)
measure: Number of Participants With Antileukemic Complete Response (CR) or Partial Response (PR)
timeFrame: 4 weeks
measure: Number of Participants With Feline McDonough Sarcoma (FMS)-Like Tyrosine Kinase 3 (FLT3) Response
timeFrame: Week 4 and Week 8
Other outcomes:
Locations:
city: Columbus
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Houston
country: United States
facility: ImClone Investigational Site
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_DIRECTOR
References: