<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03245424</url>
  </required_header>
  <id_info>
    <org_study_id>AG120-C-010</org_study_id>
    <nct_id>NCT03245424</nct_id>
  </id_info>
  <brief_title>Ivosidenib Expanded Access Program in Relapsed/Refractory AML With an IDH1 Mutation</brief_title>
  <official_title>Expanded Access Program for Ivosidenib (AG-120) Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia With an IDH1 Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Agios Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Agios Pharmaceuticals, Inc.</source>
  <brief_summary>
    <textblock>
      To provide access to ivosidenib monotherapy to patients with relapsed or refractory acute&#xD;
      myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Conduct:&#xD;
&#xD;
      Patients who are eligible for enrollment will be entered into the study. Patients will&#xD;
      receive ivosidenib 500 mg by mouth once daily on 28-day cycles until disease progression,&#xD;
      unacceptable toxicity, physician or subject decision to discontinue, the subject proceeds to&#xD;
      hematopoietic stem cell transplant, the subject dies, or until the study closes. Patients who&#xD;
      achieve complete remission, undergo stem cell transplant, and then relapse can come back onto&#xD;
      the study after consultation with the Medical Monitor. Enrollment into the study will close&#xD;
      should ivosidenib be granted marketing authorization. If the study terminates for other&#xD;
      reasons, access to drug will be assessed based on the rationale for termination.&#xD;
&#xD;
      Clinical Assessments:&#xD;
&#xD;
      All patients will have baseline assessments performed to confirm eligibility. Thereafter,&#xD;
      treatment and assessments will be per routine standard of care at the investigational site&#xD;
      and documentation will be maintained at the study site in the patient chart. Should study&#xD;
      drug be discontinued, it is recommended that the patient return at least 28 days after&#xD;
      receiving the last dose of study drug for a safety evaluation.&#xD;
&#xD;
      Safety assessments should be performed at intervals per institutional standard of care for&#xD;
      patients taking ivosidenib. These assessments should include, but are not limited to:&#xD;
      pregnancy tests, ECG, clinical lab assessments, vital signs and physical exam findings, and&#xD;
      assessment of adverse events of special interest (AESIs)/serious adverse events (SAEs).&#xD;
      Toxicity severity will be graded according to the National Cancer Institute Common&#xD;
      Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Approved for marketing</overall_status>
  <study_type>Expanded Access</study_type>
  <expanded_access_info>
    <expanded_access_type_treatment>Yes</expanded_access_type_treatment>
  </expanded_access_info>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Relapsed Adult AML</condition>
  <condition>Relapsed Pediatric AML</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ivosidenib (AG-120)</intervention_name>
    <description>Patients will receive ivosidenib 500 mg by mouth once daily on 28-day cycles</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be ≥12 years of age and weigh at least approximately 100 lbs.&#xD;
&#xD;
          2. Have AML with relapsed or refractory disease.&#xD;
&#xD;
          3. Have documented IDH1 R132 gene-mutated disease. (IDH1 mutation status will be based on&#xD;
             local evaluation.)&#xD;
&#xD;
          4. Be able to understand and willing to sign an informed assent/consent. A legally&#xD;
             authorized representative may consent on behalf of a patient who is otherwise unable&#xD;
             to provide informed consent, if acceptable to and approved by the site and/or site's&#xD;
             Institutional Review Board (IRB).&#xD;
&#xD;
          5. Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.&#xD;
&#xD;
          6. Have platelet count ≥20,000/µL. (Transfusions to achieve this level are allowed.)&#xD;
             Patients with a baseline platelet count of &lt;20,000/µL due to underlying malignancy are&#xD;
             eligible with Medical Monitor approval.&#xD;
&#xD;
          7. Have adequate hepatic function as evidenced by:&#xD;
&#xD;
               -  Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due&#xD;
                  to Gilbert's disease or leukemic involvement;&#xD;
&#xD;
               -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline&#xD;
                  phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic involvement.&#xD;
&#xD;
          8. Have adequate renal function as evidenced by:&#xD;
&#xD;
             • Creatinine clearance &gt;30 mL/min based on the Cockroft-Gault glomerular filtration&#xD;
             rate (GFR) estimation: (140 -Age) x (weight in kg) x (0.85 if female)/72 x serum&#xD;
             creatinine&#xD;
&#xD;
          9. Be recovered from any clinically relevant toxic effects of any prior surgery,&#xD;
             radiotherapy, or other therapy intended for the treatment of cancer.&#xD;
&#xD;
         10. Female patients with reproductive potential must agree to undergo medically supervised&#xD;
             pregnancy tests prior to starting study drug. The first pregnancy test will be&#xD;
             performed at screening (within 7 days prior to first study drug administration); the&#xD;
             second will be performed on the day of the first study drug administration and must be&#xD;
             confirmed negative prior to dosing. Patients with reproductive potential are defined&#xD;
             as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy&#xD;
             or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not&#xD;
             menstruated at all) for at least 24 consecutive months (i.e., has had menses at any&#xD;
             time in the preceding 24 consecutive months). Females of reproductive potential, as&#xD;
             well as fertile men and their partners who are female of reproductive potential, must&#xD;
             agree to use two effective forms of contraception (including at least one barrier&#xD;
             form) from the time of giving informed assent/consent, during the study, and for 90&#xD;
             days (both females and males) following the last dose of AG-120. Effective forms of&#xD;
             contraception are defined as hormonal oral contraceptives, injectables, patches,&#xD;
             intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal&#xD;
             ligation, condoms with spermicide, or male partner sterilization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Are eligible to participate in a clinical trial or for whom potentially curative&#xD;
             anticancer therapy is available.&#xD;
&#xD;
          2. Have previously received prior treatment with a mutant-specific IDH1 inhibitor and&#xD;
             progressed on therapy.&#xD;
&#xD;
          3. Have undergone HSCT within 60 days of the first dose of ivosidenib, or patients on&#xD;
             immunosuppressive therapy post HSCT at the time of screening, or with clinically&#xD;
             significant graft-versus-host disease (GVHD). (The use of a stable dose of oral&#xD;
             steroids post HSCT and/or topical steroids for ongoing skin GVHD is permitted with&#xD;
             Medical Monitor approval.)&#xD;
&#xD;
          4. Have received systemic anticancer therapy or radiotherapy &lt;14 days prior to their&#xD;
             first day of study drug administration. (Hydroxyurea is allowed prior to enrollment&#xD;
             and after the start of ivosidenib for the control of peripheral leukemic blasts in&#xD;
             patients with leukocytosis [white blood cell {WBC}] counts &gt;30,000/μL.)&#xD;
&#xD;
          5. Have received an investigational agent &lt;14 days prior to their first day of study drug&#xD;
             administration. In addition, the first dose of ivosidenib should not occur before a&#xD;
             period ≥5 half-lives of the investigational agent has elapsed.&#xD;
&#xD;
          6. Are taking known strong CYP3A4 inducers or sensitive CYP3A4 substrate medications with&#xD;
             a narrow therapeutic window, unless they can be transferred to other medications&#xD;
             within ≥ 5 half-lives prior to dosing or unless the medications can be properly&#xD;
             monitored during the study.&#xD;
&#xD;
          7. Are taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a&#xD;
             narrow therapeutic window, unless they can be transferred to other medications within&#xD;
             ≥5 half-lives prior to dosing or unless medications can be properly monitored during&#xD;
             the study.&#xD;
&#xD;
          8. Are pregnant or breast feeding.&#xD;
&#xD;
          9. Have an active severe infection that requires anti-infective therapy or with an&#xD;
             unexplained fever &gt;38.5°C during Screening visits or on their first day of study drug&#xD;
             administration (at the discretion of the Investigator, patients with tumor fever may&#xD;
             be enrolled).&#xD;
&#xD;
         10. Have known hypersensitivity to any of the components of ivosidenib.&#xD;
&#xD;
         11. Have had New York Heart Association Class III or IV congestive heart failure (Appendix&#xD;
             14.2), myocardial infarction, unstable angina, and/or stroke.&#xD;
&#xD;
         12. Have a heart-rate corrected QT interval using Fridericia's method (QTcF) ≥ 470 msec or&#xD;
             any other factor that increases the risk of QT prolongation or arrhythmic events&#xD;
             (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).&#xD;
             Patients with prolonged QTcF interval in the setting of bundle branch block may&#xD;
             participate in the study.&#xD;
&#xD;
         13. Have active hepatitis B or C. Patients with human immunodeficiency virus (HIV)&#xD;
             infection are allowed provided their disease is under control on anti-retroviral&#xD;
             therapy and that precautions are taken to modify their HAART regimen to minimize&#xD;
             ivosidenib drug interactions. Such subjects should be monitored for a change in dosage&#xD;
             requirements for the concomitant HAART drug when co-administering ivosidenib.&#xD;
&#xD;
         14. Have any other medical or psychological condition, deemed by the Investigator to be&#xD;
             likely to interfere with a patient's ability to sign informed assent/consent,&#xD;
             cooperate, or participate in the study.&#xD;
&#xD;
         15. Have immediately life-threatening, severe complications of leukemia such as&#xD;
             uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated&#xD;
             intravascular coagulation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>July 20, 2018</last_update_submitted>
  <last_update_submitted_qc>July 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivosidenib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03245424
org study id: AG120-C-010
nct id: NCT03245424
lead sponsor: 
To provide access to ivosidenib monotherapy to patients with relapsed or refractory acute
      myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation.
Study Conduct:

      Patients who are eligible for enrollment will be entered into the study. Patients will
      receive ivosidenib 500 mg by mouth once daily on 28-day cycles until disease progression,
      unacceptable toxicity, physician or subject decision to discontinue, the subject proceeds to
      hematopoietic stem cell transplant, the subject dies, or until the study closes. Patients who
      achieve complete remission, undergo stem cell transplant, and then relapse can come back onto
      the study after consultation with the Medical Monitor. Enrollment into the study will close
      should ivosidenib be granted marketing authorization. If the study terminates for other
      reasons, access to drug will be assessed based on the rationale for termination.

      Clinical Assessments:

      All patients will have baseline assessments performed to confirm eligibility. Thereafter,
      treatment and assessments will be per routine standard of care at the investigational site
      and documentation will be maintained at the study site in the patient chart. Should study
      drug be discontinued, it is recommended that the patient return at least 28 days after
      receiving the last dose of study drug for a safety evaluation.

      Safety assessments should be performed at intervals per institutional standard of care for
      patients taking ivosidenib. These assessments should include, but are not limited to:
      pregnancy tests, ECG, clinical lab assessments, vital signs and physical exam findings, and
      assessment of adverse events of special interest (AESIs)/serious adverse events (SAEs).
      Toxicity severity will be graded according to the National Cancer Institute Common
      Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
expanded access type treatment: Yes
intervention type: Drug
intervention name: ivosidenib (AG-120)
description: Patients will receive ivosidenib 500 mg by mouth once daily on 28-day cycles
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Ivosidenib