Clinical trial NCT02074839 (phase 1, status: recruiting)
Conditions: relapsed or refractory acute myeloid leukemia (aml), untreated aml, other idh1-mutated positive hematologic malignancies, myelodysplastic syndromes
ICD codes: D46.9, D46.C, D46.Z
Drugs: ag-120
SMILES: [H][C@@](N(C(=O)[C@]1([H])CCC(=O)N1C1=NC=CC(=C1)C#N)C1=CC(F)=CN=C1)(C(=O)NC1CC(F)(F)C1)C1=C(Cl)C=CC=C1
Eligibility criteria:

        Key Inclusion Criteria:

          -  Subject must be ≥18 years of age.

          -  Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy
             based on local or central evaluation.

          -  Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling,
             and urine sampling during the study.

          -  Subjects must have ECOG PS of 0 to 2.

          -  Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed).

          -  Subjects must have adequate hepatic function as evidenced by: Aspartate
             aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)
             ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x
             upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic
             disease

          -  Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 ×
             ULN or creatinine clearance >40mL/min based on Cockroft-Gault glomerular filtration
             rate (GFR)

          -  Subjects must be recovered from any clinically relevant toxic effects of any prior
             surgery, radiotherapy, or other therapy intended for the treatment of cancer.

          -  Female subjects with reproductive potential must have a negative serum pregnancy test
             within 7 days prior to the start of therapy and on the first day of study drug
             administration.

        Key Exclusion Criteria:

          -  Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days
             of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the
             time of screening, or with clinically significant graft-versus-host disease (GVHD).
             (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin
             GVHD is permitted.)

          -  Subjects who received systemic anticancer therapy or radiotherapy <14 days prior to
             their first day of study drug administration. (Hydroxyurea is allowed prior to
             enrollment and after the start of AG-120).

          -  Subjects who received an investigational agent <14 days prior to their first day of
             study drug administration.

          -  Subjects who are pregnant or breastfeeding.

          -  Subjects with an active severe infection or with an unexplained fever >38.5°C during
             screening visits or on their first day of study drug administration (at the discretion
             of the Investigator, subjects with tumor fever may be enrolled).

          -  Subjects with New York Heart Association (NYHA) Class III or IV congestive heart
             failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan
             within approximately 28 days of C1D1.

          -  Subjects with a history of myocardial infarction within the last 6 months of
             screening.

          -  Subjects with a known unstable or uncontrolled angina pectoris.

          -  Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.

          -  Subjects with known unstable or uncontrolled angina pectoris.

          -  Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that
             increase the risk of QT prolongation or arrhythmic events.

          -  Patients taking medications that are known to prolong the QT interval

          -  Subjects with known infection with human immunodeficiency virus (HIV) or active
             hepatitis B or C.

          -  Subjects with clinical symptoms suggesting active central nervous system (CNS)
             leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if
             there is a clinical suspicion of CNS involvement by leukemia during screening.

          -  Subjects with immediately life-threatening, severe complications of leukemia such as
             uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated
             intravascular coagulation.