Chicago, Illinois 60612


Purpose:

This is a dose escalation study to evaluate Omacetaxine when given in combination with a standard induction regimen of "7+3" (cytarabine for Days 1-7 and Idarubicin for Days 1-3) in patients with newly diagnosed acute myelogenous leukemia (AML).


Study summary:

This is a dose escalation study to evaluate Omacetaxine when given in combination with a standard induction regimen of "7+3" (cytarabine for Days 1-7 and Idarubicin for Days 1-3) in patients with newly diagnosed acute myelogenous leukemia (AML). Omacetaxine will be given subcutaneously Q12 hours on Days 1-7. The optimally safe and active dose (OD) will be determined using the EffTox design. EffTox is a Bayesian adaptive design that seeks to determine the optimal dose for further study in Phase II by considering a trade-off between efficacy and toxicity. The EffTox design begins by treating a cohort of three patients at dose level 1. These patients' efficacy and toxicity outcomes are used to update the posterior distributions for the probability of efficacy and toxicity and identify acceptable dose levels. The study terminates if no dose levels are acceptable. Otherwise, the acceptable doses are ranked using the Euclidean distance from (1.0, 0.0) and the next cohort is treated at the dose with the minimum distance under the restriction that we may only escalate or deescalate by one dose level at a time (e.g., the second cohort can only escalate to dose level 2 or deescalate to dose level -1). The second cohort is treated at the dose with the minimum distance and posterior distributions, and the list of acceptable doses and distances are updated as before. This process continues until at least 20 subjects are enrolled in the study. The dose with the minimum distance at study completion is considered the optimal dose for further investigation. If none of the dose levels are acceptable at study completion, an optimal dose level will not be identified and the drug does not warrant further investigation. Post induction therapy will consist of standard cytarabine consolidation chemotherapy or allogeneic stem cell transplantation based on pretreatment risk assessment.


Criteria:

Inclusion Criteria: 1. Newly diagnosed, untreated patients with AML according to the WHO classification for AML.18 2. Patients age 18 to 70 years old who meet diagnostic criteria for AML according to the WHO classification for AML. 3. Previously untreated AML (≥20% blasts). Note that prior short-term therapy (≤7 days) with hydroxyurea, steroids, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors, azacitidine, ATRA), or hematopoietic growth factors is allowed. A single or two-day dose of cytarabine (up to 3 g/m2) for emergency use is also allowed as prior therapy. 4. ECOG performance status of 0-3 5. Adequate organ function, if not suspected to be due to AML, within 14 days of study registration, defined as: Total bilirubin < 2.0 x ULN (unless due to hemolysis) AST and ALT < 3 X ULN (unless believed to be due to tumor involvement) Serum Creatinine ≤ 1.5 x ULN Creatinine Clearance > 30 ml/min 6. Negative urine or serum pregnancy test in females. Patients of reproductive potential (males and females) must consent to and practice double-barrier methods of contraception during treatment and for 12 weeks following the last dose of Omacetaxine. 7. Patients must be willing and able to provide informed consent Exclusion Criteria: 1. Patients with AML age 71 or older. 2. Acute promyelocytic leukemia. 3. Other investigational drug use within 4 weeks of study entry. 4. Cardiac insufficiency grade III or IV New York Heart Association (NYHA) 5. Female subjects who are pregnant or breast feeding. 6. Patients who are HIV positive. 7. Active uncontrolled infection or severe systemic infection 8. Concurrent malignancy (other than AML) with an estimated life expectancy less than two years and requiring active therapy. 9. Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up. 10. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or medically relevant active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant. 11. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study. 12. Pregnant or breastfeeding: Omacetaxine is a Pregnancy Category D medication and has caused embryo-fetal death in animals. Confirmation that the subject is not pregnant must be established by a negative urine human chorionic gonadotropin pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.


NCT ID:

NCT02440568


Primary Contact:

Principal Investigator
John Quigley, MD
University of Illinois at Chicago

John Quigley, MD
Phone: 312-413-1300 or 312-401-0539
Email: seanq@uic.edu


Backup Contact:

Email: elizj@uic.edu
Elizabeth Jeanes
Phone: 312-413-2746


Location Contact:

Chicago, Illinois 60612
United States

Elizabeth Jeanes
Phone: 312-413-2746
Email: elizj@uic.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 22, 2017

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