Clinical Trial 19446

Cancer Type:
Interventions:AG-120 (Ivosidenib); Ivosidenib

Study Type: Treatment
Phase of Study: NA
Investigators:

  • David Sallman

Overview

Study Title

Expanded Access Program for Ivosidenib (AG-120) Monotherapy in Patients with Relapsed or Refractory Acute Myeloid Leukemia with an IDH1 Mutation

Summary

The purpose of this study is to provide access to ivosidenib monotherapy to patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation.

Objective

The objective of the study is to provide access to ivosidenib monotherapy to patients with relapsed or refractory AML with an isocitrate dehydrogenase 1 (IDH1) mutation.

Inclusion Criteria

  • Be ≥12 years of age and weigh at least approximately 100 lbs.
  • Have Acute Myeloid Leukemia (AML) with relapsed or refractory disease.
  • Have documented IDH1 R132 gene-mutated disease. (IDH1 mutation status will be based on local evaluation.)
  • Be able to understand and willing to sign an informed assent/consent. A legally authorized representative may consent on behalf of a patient who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site's Institutional Review Board (IRB).
  • Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.
  • Have platelet count ≥20,000/µL. (Transfusions to achieve this level are allowed.) Patients with a baseline platelet count of oess than 20,000/µL due to underlying malignancy are eligible with Medical Monitor approval.
  • Have adequate hepatic function.
  • Have adequate renal function.:
  • Be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
  • Females with reproductive potential must agree to undergo medically supervised pregnancy tests prior to starting study drug. Females of reproductive potential, as well as fertile men and their partners who are female of reproductive potential, must agree to use two effective forms of contraception (including at least one barrier form) from the time of giving informed assent/consent, during the study, and for 90 days (both females and males) following the last dose of AG-120.

  • Exclusion Criteria

  • Are eligible to participate in a clinical trial or for whom potentially curative anticancer therapy is available.
  • Have previously received prior treatment with a mutant-specific IDH1 inhibitor and progressed on therapy.
  • 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.)
  • Have received systemic anticancer therapy or radiotherapy less than 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.)
  • Have received an investigational agent > 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.
  • 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.
  • Are pregnant or breast feeding.
  • 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).
  • Have known hypersensitivity to any of the components of ivosidenib.
  • Have had New York Heart Association Class III or IV congestive heart failure (Appendix 14.2), myocardial infarction, unstable angina, and/or stroke.
  • 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.
  • 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.
  • 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.
  • Have immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.