Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: A Pilot Study of ODSH in Acute Myeloid Leukemia

Summary: A Pilot Study of ODSH in Acute Myeloid Leukemia

Detailed description: This is an open-label, multi-center, 10 patient pilot study with an anticipated 1 year enrollment period
  Primary Objectives:
  1. To evaluate the safety and tolerability of ODSH in patients with Acute Myeloid Leukemia (AML) receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
  2. To determine whether there is preliminary evidence of an effect of ODSH on time to transfusion-independent platelet recovery in Acute Myeloid Leukemia (AML) patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
  Secondary Objectives:
  1. To determine whether there is preliminary evidence of an effect of ODSH on remission rate following cytarabine and idarubicin induction in Acute Myeloid Leukemia (AML) patients.
  2. To determine whether there is preliminary evidence of an effect of ODSH on improving platelet nadir counts in Acute Myeloid Leukemia (AML) patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
  3. To determine whether there is preliminary evidence of an effect of ODSH on decreasing the number of platelet transfusions in Acute Myeloid Leukemia (AML) patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
  4. To determine whether there is preliminary evidence of an effect of ODSH on reducing overall side effects of chemotherapy in Acute Myeloid Leukemia (AML) patients receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.
  Enrollment for newly diagnosed, previously untreated acute myeloid leukemia. Acute promyelocytic leukemia and acute megakaryoblastic leukemia subtypes are excluded.
  All patients will receive standard induction chemotherapy with cytarabine 100 mg/m2/day by continuous intravenous infusion over 24 hours daily for 7 days (D 1-7) plus idarubicin 12 mg/m2/day by intravenous injection daily for 3 days (D 1-3). For consolidation, patients younger than 60 will receive cytarabine at a dose of 3 grams/m2 over 3 hours, every 12 hours on days 1, 3, and 5.
  Induction cycle: ODSH 4 mg/kg IV bolus day 1, 30 minutes after completion of administration of the first dose of idarubicin, then ODSH 0.25 mg/kg/hour for 24 hours daily by continuous IV infusion days 1-7.
  Consolidation cycle: ODSH 4 mg/kg IV bolus day 1 administered 30 minutes after completion of infusion of the first dose of cytarabine then ODSH 0.25 mg/kg/hour for 24 hours daily by continuous IV infusion days 1-5
  7 days in induction cycle and 5 days in consolidation cycles

Eligibility: Inclusion Criteria:
  -  Newly diagnosed, previously untreated acute myeloid leukemia. Acute promyelocytic leukemia and acute megakaryoblastic leukemia subtypes are excluded
  -  No prior chemotherapy for acute myeloid leukemia; however, prior hydroxyurea to control white blood cell count is allowed
  -  Age: ≥18
  -  Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  -  Cardiac ejection fraction ≥ 50% (echocardiography or Multi-Gated Acquisition Scan [MUGA])
  -  Adequate hepatic and renal function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin and creatinine < 2.5 x upper normal limit).
  -  Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
  Exclusion Criteria:
  -  Patients with acute promyelocytic leukemia
  -  Patients with acute megakaryoblastic leukemia
  -  Patients with Central Nervous System (CNS) leukemia
  -  Presence of uncontrolled bleeding
  -  Presence of significant active infection that is uncontrolled as judged by the investigator
  -  History of severe congestive heart failure or other cardiac disease that contraindicates the use of anthracyclines, including idarubicin
  -  Pre-existing liver disease
  -  Renal insufficiency, which, in the opinion of the investigator, might adversely affect schedule and dose of therapy with cytarabine as well as management of tumor lysis syndrome. Patients with creatinine levels ≥2 mg/dl are not eligible
  -  Use of recreational drugs or history of drug addiction, within the prior 6 months
  -  Known history of positive hepatitis B surface antigens or hepatitis C virus (HCV) antibodies
  -  Known history of positive test for Human Immunodeficiency Virus (HIV) antibodies
  -  Psychiatric or neurologic conditions that could compromise patient safety or compliance, or interfere with the ability to give proper informed consent
  -  History of other active malignant disease within 5 years, other than cured basal cell carcinoma of the skin, cured in situ carcinoma of the cervix, or localized prostate cancer that has received definitive therapy. Such prostate cancer patients who are receiving hormonal therapy are eligible
  -  Presence of disseminated intravascular coagulation, as confirmed by laboratory studies demonstrating evidence of both increased thrombin generation (decreased fibrinogen, prolonged Prothrombin Time [PT] and Partial Thromboplastin Time [aPTT]) as well as increased fibrinolysis (elevated D-dimer level)
  -  Patients receiving any form of anticoagulant therapy
  -  Presence of a known bleeding disorder or coagulation abnormality
  -  Treatment with any other investigational agent within 7 days prior to study entry. All prior toxicities should have resolved to no greater than Grade 1 (with the exception of alopecia)
  -  Pregnant or breast-feeding patients
  -  Patient with childbearing potential not using adequate contraception
  -  Any condition that requires maintenance of platelet counts at 50,000/μL or higher.

Relevance to patient case: not relevant