Bortezomib and Doxil for the Treatment of Patients With Acute Myelogenous Leukemia
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Bortezomib; Doxil
Intervention description: Bortezomib will be given twice a week subcutaneously (under the skin) for two weeks in every 3 week cycle.; Doxil or LipoDox will also be given through a venous catheter (inside your vein). Doxil or LipoDox will be given over 60 to 90 minutes on Day 4 of every 21-day cycle.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Bortezomib; Doxil

Summary:

      The purpose of this study is to determine whether bortezomib in combination with
      doxil/lipodox is effective in the treatment of Acute Myeloid Leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Female subjects must be either postmenopausal for at least 1 year before the screening
             visit, is surgically sterilized or if they are of childbearing potential, agree to
             practice 2 effective methods of contraception from the time of signing the informed
             consent form through 30 days after the last dose of SQ VELCADE, or agree to completely
             abstain from heterosexual intercourse.

          -  Male subjects, even if surgically sterilized must agree to 1 of the following:
             practice effective barrier contraception during the entire study treatment period and
             through a minimum of 30 days after the last dose of study drug, or completely abstain
             from heterosexual intercourse.

          -  Adults (age 18 to 80) with AML, excluding the M3 subtype, that are not likely to
             respond to conventional therapy

          -  Bone marrow and peripheral blood studies must be available for confirmation of
             diagnosis.

          -  Performance status of 60% or greater by the Karnofsky scale

          -  A minimum of 4 weeks must have elapsed since the completion of prior chemotherapy.

          -  Patients may have had autologous transplant.

          -  There are no minimum hematological parameter requirements prior to the first two
             cycles, as patients with AML and myelodysplastic syndrome (MDS) are understood to have
             low absolute neutrophil count (ANC) and platelet counts when the disease is active.
             However, patients with white blood cell count (WBC) greater than 30,000 will receive
             hydroxyurea to reduce the WBC count to below 30,000 at which point they may begin
             treatment.

          -  A pretreatment calculated creatinine clearance (absolute value) of ≥ 40 ml/minute or
             serum creatinine of < 1.5 x upper limit of normal is required.

          -  Patients must have a serum bilirubin ≤1.5 mg/dl, serum glutamic-oxaloacetic
             transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤2.5 times the
             institutional upper limits of normal.

        Exclusion Criteria:

          -  There is no specific platelet and absolute neutrophil count that will exclude patients
             from this study given the natural history of AML.

          -  Patient has greater than or equal to Grade 2 peripheral neuropathy

          -  Patient had myocardial infarction within 6 months prior to enrollment or has New York
             Heart Association Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at screening must be documented by the investigator as not medically
             relevant. An left ventricular ejection fraction (LVEF) must be > 50

          -  Patient has hypersensitivity to VELCADE, boron, or mannitol.

          -  Female subject is pregnant or lactating.

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period, or a positive urine pregnancy test on Day 1 before first dose of
             study drug, if applicable.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial.

          -  Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
             require concurrent radiotherapy (which must be localized in its field size) should be
             deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
             date of therapy.

          -  Patients with active/uncontrolled central nervous system (CNS) leukemia

          -  Patients eligible, at the time of starting treatment, for curative therapeutic
             approaches (such as allogeneic transplant) are not eligible for the trial.

          -  Patients may not receive any other anti-cancer therapy (cytotoxic, biologic,
             radiation, or hormonal other than for replacement) while on this study other than
             hydroxyurea for control of counts.

          -  Human Immunodeficiency Virus (HIV)-positive.