A Phase I Study of IGN523 in Subjects With Relapsed or Refractory AML

Study Overview
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Brief Summary
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This study will examine the safety and tolerability of IGN523 administered as an IV infusion. The main purpose of the study is to determine the maximum tolerated dose (MTD), which is the highest dose that does not cause unacceptable side effects of IGN523 in patients with acute myeloid leukemia (AML). The MTD will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of IGN523. In addition, the pharmacokinetic profile and anti-leukemia activity of IGN523 will be assessed. A recommended Phase 2 dose (RP2D) of IGN523 will be identified, on the basis of safety, pharmacokinetic (PK), and pharmacodynamic (PD) data.

Detailed Description
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Primary Objectives: Evaluate the safety and tolerability of IGN523 administered weekly Determine the MTD and dose limiting toxicity (DLT) of IGN523 when administered weekly during the DLT Evaluation Period Identify a recommended Phase 2 dose (RP2D) of IGN523 on the basis of safety, PK, and PD data Secondary Objectives: Assess the incidence of antibody formation to IGN523 Characterize the PK of IGN523 in subjects with relapsed or refractory AML Perform a preliminary assessment of the anti-leukemic activity of IGN523 in subjects with relapsed or refractory AML Perform a preliminary assessment of biologic markers that might predict IGN523 anti-leukemic activity Estimated Enrollment: 50 Study Start Date: February 2014 Estimated Study Completion Date: March 2016 Estimated Primary Completion Date: September 2015 (Final data collection for primary outcome measure)

Official Title
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A Phase 1, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Clinical Activity of IGN523 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Conditions
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Acute Myelogenous Leukemia, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: IGN523


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or treatment-refractory AML Eastern Cooperative Oncology Group status 0-2 Life expectancy of at least 12 weeks Adequate baseline renal and hepatic function Measurable disease (eg, peripheral blasts greater than 5%) Exclusion Criteria: Chronic myelogenous leukemia in blast crisis Monoclonal therapy within 4 weeks, or chemotherapy or radiotherapy within 2 weeks Unresolved acute toxicity from prior anti-cancer therapy Prior allogeneic stem cell transplant and active graft-versus-host disease requiring systemic immunosuppressive therapy within 15 days prior to screening History of severe allergic or anaphylactic reactions to monoclonal antibody therapy Known current leptomeningeal or central nervous system (CNS) involvement of leukemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IGN523<br>IGN523 | Drug: IGN523<br>* Given intravenously every week for 8 weeks. Dosing beyond 8 weeks will be permitted for subjects meeting criteria for ongoing clinical benefit and acceptable safety.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Through 1 month following last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of antidrug antibodies to IGN523 |  | Through 6 months following last dose | 
| Blood concentrations of IGN523 |  | Through 6 months following last dose | 
| Assess anti-leukemic activity of IGN523 | Subjects with measurable disease will be assessed by standard criteria (Cheson). Subjects will be formally evaluated for response at the end of Cycle 2; additional evaluations may be performed during the study as clinical indicated. | Initial assessment after 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Drug therapy, CD98, Relapsed, Refractory, Monoclonal antibody