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A Study in Participants With Acute Leukemia

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ClinicalTrials.gov Identifier: NCT01214603
Recruitment Status : Completed
First Posted : October 5, 2010
Results First Posted : November 19, 2018
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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

Condition or disease Intervention/treatment Phase
Leukemia Drug: LY2090314 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
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 : November 2010
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012


Arm Intervention/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




Primary Outcome Measures :
  1. Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)] [ Time Frame: 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)] [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01214603


Locations
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United States, Illinois
For 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.
Chicago, Illinois, United States, 60637
United States, Minnesota
For 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.
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
For 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.
Durham, North Carolina, United States, 27710
United States, Texas
For 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.
Houston, Texas, United States, 77030
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01214603     History of Changes
Other Study ID Numbers: 13370
I2H-MC-JWYB ( Other Identifier: Eli Lilly and Company )
First Posted: October 5, 2010    Key Record Dates
Results First Posted: November 19, 2018
Last Update Posted: November 19, 2018
Last Verified: October 2018
Keywords provided by Eli Lilly and Company:
Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute
Leukemia, Leukemia
Additional relevant MeSH terms:
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Leukemia
Neoplasms by Histologic Type
Neoplasms