Phase 2 Study of LY2090314 in Patients with Acute Leukemia
The goal of this clinical research study is to learn if LY2090314 can help to control the disease in patients with AML. The safety and difference in dose levels of this drug will also be studied. LY2090314 is a drug that stops DNA (the genetic material of cells) growth in which leukemias are dependent upon for their survival.
Disease Group: Leukemia
Treatment Agent: LY2090314
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Eli Lilly and Company
The primary objective of this study is to determine if LY2090314 as monotherapy, with different frequencies of administration, may be safely administered to patients (pts) with refractory or relapsed acute myeloid leukemia (AML) or de novo AML. Secondary objectives: To characterize the safety and toxicity profile of LY2090314 To estimate the PK parameters of LY2090314 in acute and refractory leukemia patients To document any efficacy observed with LY2090314 To determine the pharmacodynamic change in b-catenin levels in peripheral blood mononuclear cells (PBMCs) and bone marrow leukemic blasts To explore other pharmacodynamic biomarkers associated with GSK-3 activity and mechanism of action.
IRB Review and Approval Date: 02/17/2012
Recruitment Status: Not Accepting
Projected Accrual: up to 38
1) Patients must have a confirmed diagnosis of one of the following:
acute myelogenous leukemia (AML) that is refractory or relapsed disease.
If patients 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
patient should not be a candidate for standard therapy and a clinical
trial is a preferred treatment option.
2) Are equal to or greater than 18 years of age.
3) Have given written informed consent prior to any study-specific procedures.
4) Have adequate organ function including: Hepatic: bilirubin less than or equal to 1.5 X the upper limit of normal (ULN). Alkaline phosphatase and transaminases (ALT and AST) less than or equal to 5 X ULN. Note: However, ALT and /or AST elevations greater than 5 X ULN maybe be acceptable with asymptomatic or clinically nonrelevant elevation of these isolated transaminases. In addition, combined AST and ALT without increases in bilirubin may be observed in patients experiencing hemolysis. In cases where elevations of AST, ALT, and/or bilirubin are noted at baseline, the patient may enter treatment as long as there is evidence that the laboratory elevations of the lever-related enzymes are not a reflection of severe hepatic impairment.
5) continuation of #4: Renal: serum creatinine less than or equal to the ULN. No known active renal disease. In rare cases, patients may enter treatment with a serum creatinine greater than the ULN as elevations of serum creatinine may be secondary to dehydration. This requires prior approval by the Lilly physician and must be consistent with the patient's history.
6) Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
7) 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 counts 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.
8) Are reliable and willing to be available for the duration of the study and are willing to follow study procedures.
9) 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.
10) 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.
11) Have an estimated life expectancy of greater than or equal to 6 weeks.
1) 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.
2) Patients with chronic myelogenous leukemia (CML) including blast crisis phase.
3) Patients with known central nervous system (CNS) leukemia by spinal fluid cytology or imaging. A lumbar puncture is not required unless CNS involvement is clinically suspected. Patients with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment.
4) Have serious pre-existing medical conditions (left to the discretion of the investigator).
5) Have one of the following abnormalities: QTcF (Fridericia corrected) interval greater than 450 msec on screening 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.
6) Have family history of long QT syndrome or sudden death due to ventricular arrhythmia.
7) Concomitant medication that may cause QTc prolongation or induce Torsades de Pointes at the time of study entry. (Refer to Appendix F)
8) Have systolic blood pressure greater than or equal to 160 mm Hg and diastolic blood pressure greater than or equal to 100 mm Hg.
9) 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 patients with a history of arrhythmia that is symptomatic or requires treatment.
10) Have uncorrected electrolyte disorders including potassium <3.4 mEq/L (<3.4 mmol/l), calcium <8.4 mg/dL (2.1 mmol/L), or magnesium <1.2 mg/dL (<0.62 mmol/L).
11) Have other active malignancy (with the exception of basal and squamous cell skin cancer) at time of study entry.
12) Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogenic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
13) Have uncontrolled systemic infection.
14) Females who are pregnant or lactating.
15) Presence of clinical evidence of viral disease caused by human immunodeficiency virus, hepatitis B, or hepatitis C. A serum positive result for presence of surface antigen antibodies or antibodies to hepatitis C virus alone does not constitute an exclusion. As required by standard medical practice, active viral disease must be determined to exclude such patients.
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