A PHASE 2 OPEN-LABEL, AC220 MONOTHERAPY EFFICACY (ACE) STUDY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) WITH FLT3-ITD ACTIVATING MUTATIONS
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 12.0Level: LLTClassification code 10000886Term: Acute myeloid leukemia
- Registration Number
- EUCTR2009-013093-41-FR
- Lead Sponsor
- Ambit Biosciences Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- 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 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. Patients with previously known or currently locally determined FLT3-ITD activating mutations prior to study entry, may be considered positive for FLT3-ITD activating mutation for eligibility prior to central laboratory confirmation of such a mutation at the discretion of the Investigator and with the agreement of the Sponsor. (Appropriate blood and bone marrow samples must be taken for FLT3-ITD determination and shipped to the Sponsor-designated laboratory prior to study entry.) However, if such a mutation is not confirmed by the central laboratory, the patient may be permitted to stay on the study if they wish and consent to do so but such patients’ data will be analyzed separately.
6. ECOG performance status of 0 to 2
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 x ULN (upper limit of normal)
11. Serum potassium, magnesium, and calcium levels 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 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 s
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. Donor lymphocyte infusion (DLI) is not permitted during the study or 30 days prior to study entry.
9. Clinically active CNS leukemia. Patients with CNS leukemia, which is controlled, but who are still receiving IT therapy at study entry may be considered eligible and continue receive IT therapy at the discretion of the Investigator and with agreement of the Sponsor.
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, 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).
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, 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 < 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 breas
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