Clinical Trials

Inclusion Criteria

• Males and females age ≥ 18 yrs
• Histologically confirmed Acute Myeloid Leukemia who have failed prior induction therapy or have relapsed after prior therapy
• Assessment of FLT3 mutation status
• Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts
  • Cohort A: Subjects with a FLT3 mutation (ITD or D835) with prior FLT3 inhibitor treatment
  • Cohort B: Subjects with a FLT3 mutation (ITD or D835) without prior FLT3 inhibitor treatment
  • Cohort C: Subjects without a FLT3 mutation at the time of enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Considered by the investigator to be an appropriate candidate for a Phase 1 clinical study
• In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of FLX925 administration will be ≥ 2 weeks for cytotoxic agents and ≥ 5 half-lives for cytotoxic/non-cytotoxic agents.
  • For  rapidly proliferative disease, use of hydroxyurea is allowed before and up to 7 days on therapy
• Clinically significant toxic effects of any prior antitumor therapy (except hydroxyurea) resolved to Grade ≤ 1 before the start of study therapy (bone marrow parameters Grade 1 to 4 permitted)
• Serum AST and ALT ≤ 3 x ULN
• Serum bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or hemolysis or considered to be related to leukemia
• Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCl) of ≥ 60 mL/hour by the Cockroft-Gault equation
• Normal coagulation profile as evidenced by PT and aPTT ≤ 1.5 x ULN
• For women of childbearing potential, negative serum pregnancy test
• Women of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study and for 30 days following the last dose
• Ability to swallow tablets without difficulty
• Willingness to comply with scheduled visits, drug administration plan, protocol-specified bone marrow biopsies
• Written informed consent must be provided

Exclusion Criteria

• Subjects with AML in their first relapse following a remission >12 months in duration
• Leukemic blast count >50,000
• Active, symptomatic central nervous system (CNS) leukemia
• History of another malignancy except for the following
  • Adequately treated local non-melanoma skin cancer
  • In situ cervical carcinoma
  • Adequately treated, papillary, non-invasive bladder cancer
  • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥ 1 year prior to start of study therapy
  • Other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years
• Clinically significant cardiovascular disease
• Significant screening electrocardiogram (ECG) abnormalities
• Significant risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation or history of significant gastrointestinal, urological, intracranial or other significant bleeding within 1 year from the start of treatment
• Significant active gastrointestinal disease that might impair absorption of study therapy
• Evidence of an ongoing, uncontrolled systemic infection or an uncontrolled local infection requiring therapy at the time of start of study therapy
• Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive
• Patients known to be positive for hepatitis B or to have active hepatitis C infection
• Any evidence of ongoing graft-versus-host disease (GVHD) in subjects with prior progenitor cell transplantation
• Pregnancy or breastfeeding
• Major surgery within 4 weeks before the start of study therapy
• Ongoing immunosuppressive therapy within 14 days prior to the start of study therapy
• Subjects currently receiving treatment with any medications that have the following potential properties and who cannot be either discontinued or switched to a different medication
  • The potential to prolong the QT interval
  • Strong CYP3A4 inhibitors
  • CYP3A4 
  • CYP2C19 
  • P glycoprotein (P-gp) 
  • Breast cancer resistance protein (BCRP) substrates having a narrow therapeutic index
• Concurrent participation in another therapeutic clinical trial
• Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial