A Study in Participants With Acute Leukemia

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01214603
Collaborator
(none)
20
Enrollment
4
Locations
1
Arm
25
Duration (Months)
5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of LY2090314 in Participants With Acute Leukemia
Study Start Date :
Nov 1, 2010
Actual Primary Completion Date :
Dec 1, 2012
Actual Study Completion Date :
Dec 1, 2012

Arms and Interventions

ArmIntervention/Treatment
Experimental: LY2090314

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
Administered intravenously

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) [Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]]

    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.

Secondary Outcome Measures

  1. Number of Participants With Best Response of Complete Response or Partial Response [Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)]

    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.

  2. Percentage of Participants With Best Response of Complete Response or Partial Response [Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)]

    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.

  3. Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] [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)]]

    AUC(0-8) was estimated from the plasma drug concentration time profile.

  4. PK: AUC From Time 0 to Infinity [AUC(0-inf)] [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)]]

    AUC(0-inf) was estimated from the plasma drug concentration time profile.

  5. PK: Maximum Concentration (Cmax) [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)]]

    Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile.

  6. Percent Change From Predose Beta (β)-Catenin Levels [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)]

    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.

  7. Number of Participants Who Died [Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.ChicagoIllinoisUnited States60637
2For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.MinneapolisMinnesotaUnited States55455
3For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.DurhamNorth CarolinaUnited States27710
4For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.HoustonTexasUnited States77030

Sponsors and Collaborators

  • Eli Lilly and Company

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214603
Other Study ID Numbers:
  • 13370
  • I2H-MC-JWYB
First Posted:
Oct 5, 2010
Last Update Posted:
Nov 19, 2018
Last Verified:
Oct 1, 2018
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailStudy had safety lead-in phase [40 milligrams (mg) LY2090314 administered using 3 treatment schedules]. Each cohort of participants had different schedule. Safety lead-in data determined if expansion phase opened to enrollment. No participant enrolled in expansion phase. Participants who completed 2 cycles of treatment considered study completers.
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on Day (D)1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Period Title: Overall Study
STARTED767
Received at Least 1 Dose of LY2090314767
COMPLETED253
NOT COMPLETED514

Baseline Characteristics

Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12Total
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.Total of all reporting groups
Overall Participants76720
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
75.3
(7.16)
61.7
(14.98)
67.6
(9.81)
68.5
(11.73)
Sex: Female, Male (Count of Participants)
Female
2
28.6%
3
50%
5
71.4%
10
50%
Male
5
71.4%
3
50%
2
28.6%
10
50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
7
100%
6
100%
7
100%
20
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
2
28.6%
2
10%
White
7
100%
6
100%
5
71.4%
18
90%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (Count of Participants)
United States
7
100%
6
100%
7
100%
20
100%

Outcome Measures

1. Primary Outcome
TitleNumber of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)
DescriptionDrug-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.
Time FrameBaseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants767
Study Drug-Related AE(s)
6
85.7%
5
83.3%
6
85.7%
Study Drug-Related SAE(s)
0
0%
2
33.3%
1
14.3%
2. Secondary Outcome
TitleNumber of Participants With Best Response of Complete Response or Partial Response
DescriptionThe 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.
Time FrameBaseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants767
CR
0
0%
0
0%
0
0%
PR
0
0%
0
0%
0
0%
3. Secondary Outcome
TitlePercentage of Participants With Best Response of Complete Response or Partial Response
DescriptionThe 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.
Time FrameBaseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants767
CR
0.0
0%
0.0
0%
0.0
0%
PR
0.0
0%
0.0
0%
0.0
0%
4. Secondary Outcome
TitlePharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)]
DescriptionAUC(0-8) was estimated from the plasma drug concentration time profile.
Time FrameCycle 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)]

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
Arm/Group TitleEntire Study Population
Arm/Group DescriptionAll participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants13
Measure Profiles14
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours per milliliter (ng*h/mL)]
898
(47)
5. Secondary Outcome
TitlePK: AUC From Time 0 to Infinity [AUC(0-inf)]
DescriptionAUC(0-inf) was estimated from the plasma drug concentration time profile.
Time FrameCycle 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)]

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
Arm/Group TitleEntire Study Population
Arm/Group DescriptionAll participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants3
Measure Profiles3
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]
963
(46.4)
6. Secondary Outcome
TitlePK: Maximum Concentration (Cmax)
DescriptionCmax is the maximum observed concentration estimated from the plasma drug concentration time profile.
Time FrameCycle 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)]

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
Arm/Group TitleEntire Study Population
Arm/Group DescriptionAll participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants20
Measure Profiles36
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]
476
(56.5)
7. Secondary Outcome
TitlePercent Change From Predose Beta (β)-Catenin Levels
DescriptionPercent 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.
Time FrameCycle 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)

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug and had a predose and at least 1 postdose β-catenin sample collected.
Arm/Group TitleEntire Study Population
Arm/Group DescriptionAll participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants18
Cycle 1, Day 1, 1 h postdose
557.4
(397.49)
Cycle 1, Day 1, 2 h postdose
513.7
(284.19)
Cycle 1, Day 1, 4 h postdose
547.6
(342.89)
Cycle 1, Day 1, 8 h postdose
285.7
(421.91)
Cycle 1, Day 1, 24 h postdose
83.6
(141.96)
Cycle 1, Day 5, 2 h postdose
817.2
(576.25)
Cycle 1, Day 8, 2 h postdose
343.2
(216.26)
Cycle 1, Day 9, 1 h postdose
736.1
(831.56)
Cycle 1, Day 9, 2 h postdose
746.5
(728.22)
Cycle 1, Day 9, 4 h postdose
684.3
(630.99)
Cycle 1, Day 9, 8 h postdose
141.2
(133.13)
Cycle 1, Day 9, 24 h postdose
9.1
(99.14)
Cycle 1, Day 12, 2 h postdose
837.8
(496.95)
Cycle 1, Day 15, 1 h postdose
362.3
(246.81)
Cycle 1, Day 15, 2 h postdose
470.6
(296.31)
Cycle 1, Day 15, 4 h postdose
575.5
(422.33)
Cycle 1, Day 15, 8 h postdose
474.2
(499.30)
Cycle 2, Day 1, 2 h postdose
429.1
(339.86)
Cycle 3, Day 1, 2 h postdose
348.5
(458.67)
Cycle 4, Day 1, 2 h postdose
408.5
(291.78)
Cycle 5, Day 1, 2 h postdose
186.3
(188.34)
Cycle 6, Day 1, 2 h postdose
80.0
(77.57)
Cycle 7, Day 1, 2 h postdose
151.3
(155.60)
Cycle 8, Day 1, 2 h postdose
418.6
(357.18)
Cycle 9, Day 1, 2 h postdose
83.1
(NA)
8. Secondary Outcome
TitleNumber of Participants Who Died
DescriptionThe 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.
Time FrameBaseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]

Outcome Measure Data

Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
Measure Participants767
Death On Study, Prior To Cycle 2 Completion
1
14.3%
0
0%
0
0%
Death On Study, Post Cycle 2 Completion
0
0%
1
16.7%
0
0%
Death During 30-Day Follow-Up
2
28.6%
1
16.7%
0
0%

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleCohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Arm/Group DescriptionLY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.
All Cause Mortality
Cohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total/ (NaN) / (NaN) / (NaN)
Serious Adverse Events
Cohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total4/7 (57.1%) 5/6 (83.3%) 6/7 (85.7%)
Blood and lymphatic system disorders
Febrile neutropenia0/7 (0%) 02/6 (33.3%) 22/7 (28.6%) 3
Splenic infarction1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Cardiac disorders
Atrial fibrillation0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Cardiac ventricular disorder0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Gastrointestinal disorders
Ileitis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Small intestinal obstruction0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Infections and infestations
Clostridial infection1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Epiglottitis0/7 (0%) 02/6 (33.3%) 20/7 (0%) 0
Lung infection0/7 (0%) 00/6 (0%) 02/7 (28.6%) 2
Necrotising fasciitis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Pneumonia fungal0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Pseudomonas infection0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Staphylococcal infection0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Injury, poisoning and procedural complications
Infusion related reaction1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Musculoskeletal and connective tissue disorders
Flank pain1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Nervous system disorders
Haemorrhagic stroke1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Syncope0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Vascular disorders
Hypertension0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Other (Not Including Serious) Adverse Events
Cohort 1, 40 mg LY2090314: D1, D8, D15Cohort 2, 40 mg LY2090314: D1, D5, D9Cohort 3, 40 mg LY2090314: D1, D5, D9, D12
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total7/7 (100%) 6/6 (100%) 7/7 (100%)
Blood and lymphatic system disorders
Anaemia1/7 (14.3%) 12/6 (33.3%) 21/7 (14.3%) 1
Disseminated intravascular coagulation0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Thrombocytopenia2/7 (28.6%) 20/6 (0%) 00/7 (0%) 0
Cardiac disorders
Atrial flutter0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Left ventricular dysfunction0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Eye disorders
Cataract0/7 (0%) 01/6 (16.7%) 11/7 (14.3%) 1
Eye disorder0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Eye pain0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Halo vision1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Retinal exudates0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Vision blurred1/7 (14.3%) 10/6 (0%) 01/7 (14.3%) 1
Vitreous detachment0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Gastrointestinal disorders
Abdominal distension0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Abdominal pain1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Abdominal pain upper0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Ascites0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Constipation1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Diarrhoea2/7 (28.6%) 22/6 (33.3%) 20/7 (0%) 0
Dry mouth2/7 (28.6%) 22/6 (33.3%) 20/7 (0%) 0
Dyspepsia1/7 (14.3%) 11/6 (16.7%) 11/7 (14.3%) 1
Dysphagia1/7 (14.3%) 12/6 (33.3%) 20/7 (0%) 0
Faeces discoloured0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Gastrooesophageal reflux disease1/7 (14.3%) 11/6 (16.7%) 10/7 (0%) 0
Gingival bleeding0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Gingival blister0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Gingival pain0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Haemorrhoids0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Mouth haemorrhage0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Nausea3/7 (42.9%) 41/6 (16.7%) 13/7 (42.9%) 4
Oral pain0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Proctalgia0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Vomiting1/7 (14.3%) 12/6 (33.3%) 21/7 (14.3%) 1
General disorders
Asthenia1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Catheter site pain1/7 (14.3%) 10/6 (0%) 01/7 (14.3%) 1
Chest discomfort0/7 (0%) 02/6 (33.3%) 30/7 (0%) 0
Chest pain1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Chills0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Cyst1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Fatigue3/7 (42.9%) 31/6 (16.7%) 12/7 (28.6%) 2
Influenza like illness0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Malaise1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Mucosal inflammation0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Nodule0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Oedema peripheral1/7 (14.3%) 13/6 (50%) 32/7 (28.6%) 2
Pyrexia1/7 (14.3%) 10/6 (0%) 01/7 (14.3%) 1
Systemic inflammatory response syndrome0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Infections and infestations
Cellulitis0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Epiglottitis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Oral candidiasis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Paronychia0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Rhinitis1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Staphylococcal infection0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Upper respiratory tract infection0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Injury, poisoning and procedural complications
Arthropod bite0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Contusion1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Wound0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Investigations
Blood creatinine increased0/7 (0%) 02/6 (33.3%) 20/7 (0%) 0
Blood fibrinogen decreased0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Electrocardiogram qt prolonged0/7 (0%) 01/6 (16.7%) 12/7 (28.6%) 3
International normalised ratio increased0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Platelet count decreased0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Weight decreased0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Metabolism and nutrition disorders
Decreased appetite4/7 (57.1%) 41/6 (16.7%) 12/7 (28.6%) 2
Dehydration1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Hyperglycaemia1/7 (14.3%) 11/6 (16.7%) 20/7 (0%) 0
Hypernatraemia0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Hypoalbuminaemia0/7 (0%) 02/6 (33.3%) 20/7 (0%) 0
Hypocalcaemia0/7 (0%) 02/6 (33.3%) 20/7 (0%) 0
Hypokalaemia2/7 (28.6%) 23/6 (50%) 40/7 (0%) 0
Hypomagnesaemia0/7 (0%) 02/6 (33.3%) 30/7 (0%) 0
Hyponatraemia0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Hypophosphataemia0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia1/7 (14.3%) 10/6 (0%) 01/7 (14.3%) 1
Back pain0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Bone pain0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Joint stiffness0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Muscle spasms1/7 (14.3%) 11/6 (16.7%) 10/7 (0%) 0
Musculoskeletal chest pain0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Pain in extremity0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Nervous system disorders
Dizziness1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Dysgeusia1/7 (14.3%) 11/6 (16.7%) 11/7 (14.3%) 1
Headache0/7 (0%) 01/6 (16.7%) 11/7 (14.3%) 1
Paraesthesia1/7 (14.3%) 11/6 (16.7%) 10/7 (0%) 0
Sinus headache0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Psychiatric disorders
Anxiety0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Confusional state0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Depression0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Insomnia1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Renal and urinary disorders
Dysuria0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Haematuria1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Renal failure1/7 (14.3%) 11/6 (16.7%) 10/7 (0%) 0
Reproductive system and breast disorders
Scrotal pain0/5 (0%) 01/3 (33.3%) 10/2 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Cough0/7 (0%) 02/6 (33.3%) 22/7 (28.6%) 3
Dyspnoea2/7 (28.6%) 20/6 (0%) 01/7 (14.3%) 1
Dyspnoea exertional1/7 (14.3%) 10/6 (0%) 01/7 (14.3%) 1
Epistaxis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Nasal congestion0/7 (0%) 03/6 (50%) 30/7 (0%) 0
Oropharyngeal discomfort0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Oropharyngeal pain0/7 (0%) 01/6 (16.7%) 20/7 (0%) 0
Pleuritic pain0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Productive cough1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Respiratory failure0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Rhinitis allergic0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Tachypnoea0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Wheezing0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Skin and subcutaneous tissue disorders
Dry skin1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Hyperhidrosis1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Night sweats0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Petechiae0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Pruritus1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Pruritus generalised0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Rash maculo-papular1/7 (14.3%) 10/6 (0%) 00/7 (0%) 0
Rash papular0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Rash pruritic0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Skin mass0/7 (0%) 00/6 (0%) 01/7 (14.3%) 1
Skin ulcer0/7 (0%) 02/6 (33.3%) 30/7 (0%) 0
Vascular disorders
Deep vein thrombosis0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Embolism0/7 (0%) 01/6 (16.7%) 10/7 (0%) 0
Haematoma2/7 (28.6%) 20/6 (0%) 00/7 (0%) 0
Hypotension0/7 (0%) 02/6 (33.3%) 21/7 (14.3%) 1

Limitations/Caveats

An interim data review was performed after 6 participants in the safety lead-in completed 1 cycle of therapy. Based on the interim safety results, the expansion cohort was not opened to enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/TitleChief Medical Officer
OrganizationEli Lilly and Company
Phone800-545-5979
Email
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214603
Other Study ID Numbers:
  • 13370
  • I2H-MC-JWYB
First Posted:
Oct 5, 2010
Last Update Posted:
Nov 19, 2018
Last Verified:
Oct 1, 2018