A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome
Condition: Myelodysplastic Syndromes, Myelogenous Leukemia, Acute
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: cytarabine; vismodegib
Intervention description: Cohort 2: 20 mg sc daily for 10 days starting Day 1, with a possible further cycle of 20 mg sc daily for 5 days starting no earlier than Day 29; Cohorts 1 and 2: 150 mg orally daily
Intervention MeSH terms: Cytarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will assess the safety and efficacy of vismodegib in patients with
      relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk
      myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150
      mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in
      combination with cytarabine 20 mg subcutaneously for 10 days.

      Anticipated time on study treatment is until disease progression, intolerable toxicity, or
      patient withdrawal of consent.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients, >/= 18 years of age

          -  Patients with documented relapsed or refractory AML, except acute promyelocytic
             leukemia (APL [M3 subtype]), or relapsed or refractory high-risk MDS (high-risk MDS
             defined as International Prognostic Scoring System (IPSS) Int-2 or high and >/= 10%
             blasts in bone marrow)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Negative serum pregnancy test for women of childbearing potential and use of two forms
             of contraception while enrolled in the study and for 7 months after the patient
             discontinues from study

          -  Male patients with female partners of childbearing potential must agree to use a latex
             condom and to advise their female partner to use an additional method of contraception
             during the study and for 2 months after the last dose of vismodegib

          -  All non-hematological adverse events of any prior chemotherapy, surgery, or
             radiotherapy must have resolved to National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI CTCAE) Grade </= 2 prior to starting therapy

          -  Adequate hepatic and renal function

        Exclusion Criteria:

          -  Prior treatment with a Hh pathway inhibitor

          -  Prior therapy for the treatment of malignancy within 14 days of Day 1, with the
             exception of:

        Hydroxyurea in patients who need to continue this agent to maintain white blood cell (WBC)
        counts </= 50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study

          -  Current evidence of active central nervous system (CNS) leukemia

          -  Any other active malignancy (except non-melanoma skin cancer or carcinoma in situ of
             the cervix)

          -  Any severe and/or uncontrolled medical conditions or other conditions that could
             affect their participation in the study such as:

        Unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication
        (does not include stable, lone atrial fibrillation), or myocardial infarction </= 6 months
        before study treatment start Any active (acute or chronic) or uncontrolled
        infection/disorders that impair the ability to evaluate the patient or for the patient to
        complete the study

          -  Pregnant or breast-feeding women

          -  Patients who refuse to potentially receive blood products and/or have a severe
             hypersensitivity to blood products