Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

Launched by INSTITUT DE RECHERCHES INTERNATIONALES SERVIER · Feb 27, 2014

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called AG-120, which is taken by mouth, for patients with certain blood cancers that have a specific gene mutation called IDH1. The trial aims to find out how safe AG-120 is, how it works in the body, and its effectiveness in treating advanced types of blood cancers like relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes. The study will be conducted in two parts: the first part will test different doses of AG-120 to identify the highest dose that patients can tolerate, while the second part will give a selected dose to more patients to see how well it works and if it’s safe.

To be eligible for the trial, participants must be at least 18 years old and have a confirmed IDH1 mutation in their blood cancer. They should also be able to undergo certain tests, like bone marrow biopsies, and have a certain level of overall health. Participants can expect to be on the study treatment until their disease progresses or if they experience severe side effects. This trial is currently recruiting participants, and it's important for interested individuals to discuss their eligibility with their healthcare provider.

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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.