Clinical Trials /

Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation

NCT02492737

Description:

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation

Related Conditions:
  • Leukemia
  • Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an <span class="go-doc-concept go-doc-biomarker">IDH1</span> and/or <span class="go-doc-concept go-doc-biomarker">IDH2</span> <span class="go-doc-concept go-doc-keyword">Mutation</span>

Title

  • Brief Title: Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
  • Official Title: A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
  • Clinical Trial IDs

    NCT ID: NCT02492737

    ORG ID: AG881-C-001

    Trial Conditions

    Acute Myeloid Leukemia (AML)

    Myelodysplastic Syndrome

    Hematologic Malignancies

    Trial Interventions

    Drug Synonyms Arms
    AG881 AG881

    Trial Purpose

    The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics,
    pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that
    harbor an IDH1 and/or IDH2 mutation

    Detailed Description

    The first portion of the study is a dose escalation phase where cohorts of patients will
    receive ascending oral doses of AG-881 to determine maximum tolerated dose (MTD) and/or the
    recommended Phase II dose. The second portion of the study is a dose expansion phase where
    patients will receive AG-881 to further evaluate the safety, tolerability, and clinical
    activity of the recommended Phase II dose. Anticipated time on study treatment is until
    disease progression or unacceptable toxicity occurs or the patient is removed at the
    discretion of the investigator.

    Trial Arms

    Name Type Description Interventions
    AG881 Experimental AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion AG881

    Eligibility Criteria

    Inclusion Criteria:

    Patients must be 18 years of age

    Patients must have documented IDH1 and/or IDH2 gene-mutated disease

    Patients must have an advanced hematologic malignancy with an IDH1 and/or IDH2 mutation

    Patient must be able to understand and willing to sign an informed consent

    Patients must have ECOG PS of 0 to 2

    Patients must have adequate hepatic function as evidenced by serum total bilirubin 1.5
    upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic
    involvement

    Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase
    (ALP) 3.0 ULN, unless considered due to involvement by the neoplasm under consideration
    for treatment

    Patients must have adequate renal function as evidenced by a serum creatinine 2.0 ULN
    or Creatinine clearance 40 mL/min based on the Cockroft-Gault glomerular filtration rate
    (GFR) estimation

    Patients must be recovered from any clinically relevant toxic effects of any prior
    surgery, radiotherapy, or other therapy intended for the treatment of cancer

    Female patients with reproductive potential must have a negative serum pregnancy test
    within 7 days prior to the start of therapy. Patients with reproductive potential are
    defined as sexually mature women who have not undergone a hysterectomy, bilateral
    oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who
    have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at
    any time in the preceding 24 consecutive months)

    Exclusion Criteria:

    Patients who have undergone HSCT within 60 days

    Patients who received systemic anticancer therapy or radiotherapy <14 days prior to their
    first day of study drug administration

    Patients who received an investigational agent <14 days prior

    Patients who are pregnant or breast feeding

    Patients with an active severe infection that require anti-infective therapy or with an
    unexplained fever >38.5C 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)

    Patients 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

    Patients with a history of myocardial infarction within the last 6 months

    Patients with known unstable or uncontrolled angina pectoris

    Patients with a known history of severe and/or uncontrolled ventricular arrhythmias

    Patients with heart-rate corrected QT using Bazett's formula (QTcB) interval 480 msec or
    with other factors that increase the risk of QT prolongation or arrhythmic events

    Patients taking medications that are known to prolong the QT interval

    Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis
    B or C

    Patients 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

    Patients with immediately life-threatening, severe complications of hematologic
    malignancies such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or
    disseminated intravascular coagulation

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety/tolerability; incidence of adverse events

    Maximum Tolerated Dose and/or the recommended Phase II dose of AG-881 in patients with advanced hematologic malignancies

    Secondary Outcome Measures

    Pharmacokinetics of AG-881 in patients with advanced hematologic malignancies

    Pharmacodynamic levels of AG-881

    Pharmacodynamic levels of 2-HG

    Clinical Activity according to the 2003 revised IWG criteria for AML, the 2006 modified IWG criteria for MDS, disease-specific response criteria for other hematologic malignancies

    Trial Keywords

    acute myeloid leukemia

    AML

    myelodysplastic syndrome

    MDS

    dual mutation

    MPN

    AITL

    hematologic malignancies

    IDH1

    IDH2

    AG-881