Study of LY573636-sodium in Essential Thrombocythemia and Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia; Essential Thrombocythemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Thrombocytosis; Thrombocythemia, Essential
Intervention: LY573636-sodium
Intervention description: Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Dosing will be done on Day 1 of a 35-day cycle for acute myeloid leukemia (AML) and Day 1 of a 28-day cycle for essential thrombocythemia (ET) for at least one cycle. A participant may have additional cycles of LY573636 if he or she is receiving benefit from the study drug and does not fulfill any of the criteria for study discontinuation.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia; Myeloid Leukemia; Relapsed; Refractory

Summary:

      The purpose of this study is to determine a safe dose of LY573636-sodium to be given to
      patients with acute myeloid leukemia and to determine any side effects that may be associated
      with LY573636-sodium in this patient population. Efficacy measures will also be used to
      assess the activity of LY573636-sodium in acute myeloid leukemia and essential
      thrombocythemia patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants who have a diagnosis of either essential thrombocythemia or acute myeloid
             leukemia that is relapsed or refractory to at least one prior standard treatment. If
             participants have acute promyelocytic leukemia, they must be resistant and/or
             intolerant of both all trans retinoic acid (ATRA) and arsenic trioxide.

          -  Are at least 18 years of age.

          -  Have given written informed consent approved by Lilly and the ethical review board
             (ERB)/institutional review board (IRB) governing the site.

          -  Must have adequate hepatic and renal function.

          -  Have discontinued all previous therapies for cancer, including chemotherapy,
             radiotherapy, immunotherapy, cancer-related hormonal therapy, or other investigational
             therapy for at least 21 days for myelosuppressive agents (such as cytarabine,
             daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents
             prior to receiving study drug and recovered from the acute effects of therapy.
             Hydroxyurea used to control peripheral blood blast count is permitted within these
             respective periods, but it must be stopped at least 24 hours before study drug
             administration.

          -  Males and females with reproductive potential must agree to use medically approved
             contraceptive precautions during the trial and for 6 months following the last dose of
             study drug.

          -  Females of child bearing potential must have had a negative serum pregnancy test less
             than or equal to 7 days prior to the first dose of study drug.

          -  Have a serum albumin level greater than equal to 3.0 grams/deciliter (g/L), less than
             or equal to 72 hour prior to dosing with LY573636-sodium.

        Exclusion Criteria:

          -  Have received treatment with a drug that has not received regulatory approval for any
             indication within 14 or 21 days of the initial dose of study drug for a
             non-myelosuppressive or myelosuppressive agent, respectively.

          -  Participants with myeloproliferative disorders (for example, chronic myeloid leukemia
             (CML), polycythemia vera and primary myelofibrosis) other than essential
             thrombocythemia.

          -  Have received an autologous or allogenic stem cell transplant within 75 days of the
             initial dose of study drug for the dose escalation phase or within 60 days of the
             initial dose of study drug for the dose confirmation phase. Recipients of an
             allogeneic stem cell transplant must have discontinued immunosuppressive therapy at
             least 24 hours before study drug administration with no more than Grade 1 acute
             graft-versus-host disease.

          -  Have previously completed or withdrawn from this study or any other study
             investigating LY573636 sodium.

          -  Have serious preexisting medical conditions that in the opinion of the investigator
             would preclude participation in this study.

          -  Have serious concomitant disorders, including active bacterial, fungal, or viral
             infection, incompatible with the study.

          -  Have a second primary malignancy that could affect interpretation of results.

          -  Have a known coagulopathy or bleeding disorder, other than leukemic related
             thrombocytopenia. Participants with severe or life-threatening bleeding refractory to
             platelet transfusions are also excluded from this study.

          -  Major surgery within 4 weeks of study enrollment.

          -  Are receiving warfarin (Coumadin).

          -  Females who are pregnant or breast feeding.

          -  Have known positive results of human immunodeficiency virus (HIV), hepatitis B surface
             antigen (HBSAg) or hepatitis C antibodies (HCAb).

          -  Have received treatment within 28 days of the initial dose of study drug with an
             experimental agent for noncancerous indications that has not received regulatory
             approval for any indication.

          -  Participants receiving amiodarone, quinidine, propofol, or clozapine.

          -  Participants receiving treatment with strong or moderate inhibitors of cytochrome P450
             (CYP)2C19, including proton-pump inhibitors (PPIs). Esomeprazole or pantoprazole are
             allowed if not administered within 72 hours before or after LY573636 administration