A PHASE 2 OPEN-LABEL, AC220 MONOTHERAPY EFFICACY (ACE) STUDY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) WITH FLT3-ITD ACTIVATING MUTATIONS - ND

• Conditions: Acute Myeloid Leukemia; MedDRA version: 9.1Level: LLTClassification code 10000880

• Registration Number: EUCTR2009-013093-41-IT
• Lead Sponsor: AMBIT BIOSCIENCES CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-12
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Males and females age ≥ 18 years 2. Understand and voluntarily sign the informed consent form for this study 3. Available for periodic follow-up at the investigative site 4. Able to swallow the liquid study drug 5. Morphologically documented primary AML or AML secondary to myelodsyplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, central laboratory and must be: ≥ 60 years of age who are relapsed after 1 first-line chemotherapy regimen (with or without consolidation) and after first complete remission (CR1) < 12 months or are primary refractory to first-line chemotherapy, or ≥ 18 years of age who are relapsed or refractory after 1 second line (salvage) regimen or relapsed or refractory after HSCT Positive for FLT3-ITD activating mutation determined during current disease by the Sponsor-designated central laboratory using predefined criteria prior to study entry. 6. ECOG performance status of 0 to 2 (Appendix 4) 7. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents, including immunosuppressive therapy post HSCT. 8. Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1. 9. Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220. 10. Serum creatinine ≤ 1.5  ULN (upper limit of normal) 11. Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits. 12. Total serum bilirubin ≤ 1.5  ULN (upper limit of normal) 13. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5  ULN 14. Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if their sexual partners are women of child bearing potential (WOCBP). 15. WOCBP must be using an adequate and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 3 months after the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor 2. Diagnosis of acute promyelocytic leukemia 3. Diagnosis of chronic myelogenous leukemia (CML) in blast crisis 4. Do not have FLT3-ITD activating mutation 5. AML in relapse or refractory after 3 or more previous lines of chemotherapy treatment (ie, first-line chemotherapy with or without consolidation [first line], first salvage [second line], and second salvage [third line] or subsequent regimens) 6. AML or antecedent MDS secondary to prior chemotherapy 7. Persistent clinically significant nonhematological toxicity that is Grade > 1 by NCI CTCAE v4 from prior chemotherapy 8. Patients who have had HSCT and are within 100 days of transplant and/or are still taking immunosuppressive drugs and/or have clinically significant graft-versus-host disease requiring treatment and/or have Grade > 1 persistent nonhematological toxicity related to the transplant. 9. Clinically active CNS leukemia. 10. Patients who have previously received AC220 11. Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment) 12. Major surgery within 4 weeks prior to enrollment in the study 13. Radiation therapy within 4 weeks prior to, or concurrent with, study 14. Use of concomitant drugs that prolong QT/QTc interval or are CYP3A4 inhibitors are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient, 15. Uncontrolled or significant cardiovascular disease, including : A myocardial infarction within 12 months Uncontrolled angina within 6 months Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, Diagnosed or suspected congenital long QT syndrome Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes [TdP]); any history of arrhythmia will be discussed with the Sponsor s Medical Monitor prior to patient s entry into the study. Prolonged QTcF interval on pre-entry ECG (≥450 ms) Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker) Heart rate < 50/minute on pre-entry ECG Uncontrolled hypertension Obligate need for a cardiac pacemaker Complete left bundle branch block Atrial fibrillation 16. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy for the entire study period and for at least 3 months after the study 17. Women who are pregnant or breastfeeding 18. WOCBP with a positive pregnancy test 19. Men who are unwilling or unable to use an acceptable method of birth control 20. Active uncontrolled infection 21. Known infection with human immunodeficiency virus (HIV) 22. Known active hepatitis B or C or other active liver disease

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified