Ivosidenib Expanded Access Program in Relapsed/Refractory AML With an IDH1 Mutation

Exclusion Criteria

• •1. Are eligible to participate in a clinical trial or for whom potentially curative anticancer therapy is available.
• •2. Have previously received prior treatment with a mutant-specific IDH1 inhibitor and progressed on therapy.
• •3. Have undergone HSCT within 60 days of the first dose of ivosidenib, or patients 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 steroids for ongoing skin GVHD is permitted with Medical Monitor approval.)
• •4. Have 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 ivosidenib for the control of peripheral leukemic blasts in patients with leukocytosis \[white blood cell {WBC}\] counts \>30,000/μL.)
• •5. Have received an investigational agent \<14 days prior to their first day of study drug administration. In addition, the first dose of ivosidenib should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
• •6. Are taking known strong CYP3A4 inducers or sensitive CYP3A4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing or unless the medications can be properly monitored during the study.
• •7. Are taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥5 half-lives prior to dosing or unless medications can be properly monitored during the study.
• •8. Are pregnant or breast feeding.
• •9. Have an active severe infection that requires anti-infective therapy 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, patients with tumor fever may be enrolled).
• •10. Have known hypersensitivity to any of the components of ivosidenib.
• •11. Have had New York Heart Association Class III or IV congestive heart failure (Appendix 14.2), myocardial infarction, unstable angina, and/or stroke.
• •12. Have a heart-rate corrected QT interval using Fridericia's method (QTcF) ≥ 470 msec or any other factor that increases the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Patients with prolonged QTcF interval in the setting of bundle branch block may participate in the study.
• •13. Have active hepatitis B or C. Patients with human immunodeficiency virus (HIV) infection are allowed provided their disease is under control on anti-retroviral therapy and that precautions are taken to modify their HAART regimen to minimize ivosidenib drug interactions. Such subjects should be monitored for a change in dosage requirements for the concomitant HAART drug when co-administering ivosidenib.
• •14. Have any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed assent/consent, cooperate, or participate in the study.
• •15. Have immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.