A Study in Participants With Acute Leukemia

Study Overview
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Brief Summary
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This study is a multicenter, non-randomized, open-label, Phase 2 study of intravenous LY2090314 in participants with acute leukemia.

Official Title
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A Phase 2 Study of LY2090314 in Participants With Acute Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: LY2090314


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have confirmed diagnosis of one of the following: Acute myelogenous leukemia (AML) that is refractory or relapsed disease. If participants have acute promyelocytic leukemia (APL), they must have received prior all-trans retinoic acid and arsenic trioxide unless ineligible or intolerant to them Untreated AML (de novo or arising from a myelodysplastic syndrome). In the opinion of the investigator, the participant should not be a candidate for standard therapy and a clinical trial is a preferred treatment option Have given written informed consent prior to any study-specific procedures Have adequate organ function including: Hepatic: Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN). Alkaline phosphatase (ALP) and transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] less than or equal to 5 times ULN Renal: Serum creatinine less than or equal to the ULN. No known active renal disease. In rare cases, participants may enter treatment with a serum creatinine greater than the ULN as elevations of serum creatinine may be secondary to dehydration Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued all previous approved therapies for acute leukemia, including chemotherapy for at least 14 days, and recovered from the acute effects of therapy. Hydroxyurea used to control peripheral blast count is permitted within the first 2 cycles of treatment on study, but it must be stopped at least 24 hours before study drug administration in Cycle 3 Are reliable and willing to be available for the duration of the study and are willing to follow study procedures Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug Females with childbearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug Have an estimated life expectancy of greater than or equal to 6 weeks Exclusion Criteria: Have received treatment within 14 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication Participants with chronic myelogenous leukemia (CML) including blast crisis phase Participants with known central nervous system (CNS) leukemia by spinal fluid cytology or imaging Have serious pre-existing medical conditions (left to the discretion of the investigator) Have one of the following abnormalities: QTc (Fridericia corrected) interval >450 milliseconds (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long QT syndrome, previous history of ventricular tachycardia or unexplained syncope, left bundle branch block, or chronic atrial fibrillation Have family history of long QT syndrome or sudden death due to ventricular arrhythmia Concomitant medication that may cause QTc prolongation or induce Torsades de Pointes at the time of study entry Have systolic blood pressure greater than or equal to 160 millimeter of mercury (mm Hg) and diastolic blood pressure greater than or equal to 100 mm Hg Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher or participants with a history of arrhythmia that is symptomatic or requires treatment Have uncorrected electrolyte disorders including potassium Have other active malignancy (with the exception of basal and squamous cell skin cancer) at time of study entry Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug Have uncontrolled systemic infection Females who are pregnant or lactating Presence of clinical evidence of viral disease caused by human immunodeficiency virus, hepatitis B, or hepatitis C

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2090314<br>Cohort 1: 40 milligrams (mg) LY2090314 administered on Days 1, 8, and 15 of a 28-day cycle for at least two (2) 28-day cycles. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met. Due to a protocol amendment on September 2010, the study added 2 additional treatment schedules/cohorts. Cohort 2: 40 mg dose given on Days 1, 5, and 9 of a 21-day cycle. Cohort 3: 40 mg dose given on Days 1, 5, 9, and 12 of a 21-day cycle. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met. | Drug: LY2090314<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Response of Complete Response or Partial Response | The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/Liter (L) and absolute neutrophil count (ANC) ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) | 
| Percentage of Participants With Best Response of Complete Response or Partial Response | The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/L and ANC ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=[(number of participants with CR or PR)/(number of participants treated)]*100. | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) | 
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] | AUC(0-8) was estimated from the plasma drug concentration time profile. | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | 
| PK: AUC From Time 0 to Infinity [AUC(0-inf)] | AUC(0-inf) was estimated from the plasma drug concentration time profile. | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | 
| PK: Maximum Concentration (Cmax) | Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile. | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | 
| Percent Change From Predose Beta (β)-Catenin Levels | Percent change=[(β-catenin level postdose-predose level)/(predose β-catenin levels)]*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1. | Cycle 1: D1 and D9 (predose, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion started); Cycle 1: D5, D8, and D12 and C2 through C9: D1 (predose, 2 h after infusion started); Cycle 1: D15 (predose, 1 h, 2 h, 4 h, and 8 h after infusion started) | 
| Number of Participants Who Died | The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported. | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] | 

 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, Acute, Leukemia, Leukemia