The study is designed to determine the efficacy of AC22O in patients with Acute Myeloid Leukemia (AML) with and without FLT3-ITD activating mutations. AML is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 14.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-013093-41-GB
- Lead Sponsor
- Ambit Biosciences Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 333
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, as determined by pathology review at the treating institution, and confirmed later by the Sponsor-designated central laboratory. Patients must also meet the
following criteria
•= 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
•Must provide a sample for determination of FLT3-ITD mutation status as outlined
in Section 10.6.1.
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. The use of chemotherapeutic or antileukemic agents other than hydroxyurea (as defined in the protocol) is not permitted during the study with the possible exception of intrathecal (IT) therapy for patients with CNS leukemia in remission at the discretion of the Investigator and with the agreement of the Sponsor.
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) and glomerular filtration rate (GFR)> 30 mL/min (calculated by Cockcroft and Gault formula, Appendix 6).
11. Serum potassium, magnesium, and calcium levels (corrected serum calcium values for hypoalbunemia should be used) should be at least within institutional normal limits, and every effort should be made to keep potassium concentrations above 4.0 mEq/dL, magnesium concentrations above 1.8 mg/dL, and serum calcium at normal concentration (corrected serum calcium values for hypoalbunemia are acceptable) with the administration of oral/IV potassium and/or magnesium and/or calcium replacement during the study. If this is not possible, potassium and magnesium (and calcium) concentrations should at least be kept within institutional normal limits.
12. Total serum bilirubin = 1.5 x ULN (upper limit of normal)
13. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) = 2.5 x 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
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. 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)
5. AML or antecedent MDS secondary to prior chemotherapy
6. Persistent clinically significant nonhematological toxicity that is Grade > 1 by NCI CTCAE v4 from prior chemotherapy
7. 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. Donor lymphocyte infusion (DLI) is not permitted during the study or 30 days prior to study entry.
8. Clinically active CNS leukemia. If CNS leukemia is controlled and patients are receiving IT therapy at study entry, patients may be considered eligible at the discretion of the Investigator and with agreement of the Sponsor. Patients should continue to receive IT therapy as clinically indicated.
9. Patients who have previously received AC220
10. Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment)
11. Major surgery within 4 weeks prior to enrollment in the study
12. Radiation therapy within 4 weeks prior to, or concurrent with, study
13. 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, but only if clinically indicated and must be fully documented in the CRF (recommended washout of 5 half-lives prior to patient’s first dose with AC220).
14. 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, unless an echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is = 45% (or institutional lower limit of normal value).
• 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 <
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method