Clinical Trial Finder

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.

Arms

Experimental: AG-120

AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.

Interventions

Drug: - AG-120

AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle. Subjects may continue treatment with AG-120 until disease progression, development of other unacceptable toxicity or hematopoietic stem cell transplant.