Clinical trial NCT01214603: A Study in Participants With Acute Leukemia
Official title: A Phase 2 Study of LY2090314 in Participants With Acute Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute
Leukemia, Leukemia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-10-05
Enrollment: 20
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: This study is a multicenter, non-randomized, open-label, Phase 2 study of intravenous LY2090314 in participants with acute leukemia.


Eligibility 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

Primary outcomes:
measure: Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)
timeFrame: Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]
Secondary outcomes:
measure: Number of Participants With Best Response of Complete Response or Partial Response
timeFrame: Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)
measure: Percentage of Participants With Best Response of Complete Response or Partial Response
timeFrame: Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)
measure: Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)]
timeFrame: 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)]
measure: PK: AUC From Time 0 to Infinity [AUC(0-inf)]
timeFrame: 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)]
measure: PK: Maximum Concentration (Cmax)
timeFrame: 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)]
measure: Percent Change From Predose Beta (β)-Catenin Levels
timeFrame: 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)
measure: Number of Participants Who Died
timeFrame: Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]
Other outcomes:
Locations:
city: Chicago
country: United States
facility: 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.
state: Illinois
city: Minneapolis
country: United States
facility: 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.
state: Minnesota
city: Durham
country: United States
facility: 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.
state: North Carolina
city: Houston
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: