Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)
Condition: Myeloid Leukemia, Chronic; Myeloid Leukemia, Chronic, Accelerated-Phase; Blast Phase; Myeloid Leukemia, Chronic, Chronic-Phase
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Chronic Disease
Intervention: Homoharringtonine; Imatinib Mesylate
Intervention description: Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous (IV) infusion daily on Days 1-5 of each 4 week treatment cycle. Participants who do not achieve a meaningful hematologic or cytogenetic response by the end of the fourth cycle are discontinued from the study. Otherwise, participants may continue additional cycles of this combined treatment for a maximum of 12 cycles.
Participants who achieved a molecular or cytogenetic response, or a complete hematologic remission (CHR), could undergo subsequent cycles with a maintenance schedule of homoharringtonine 2.5 mg/m^2 by continuous 24-hour IV infusion daily for 2 days every 4 weeks. Dose escalations in subsequent cycles were allowed by one day at a time if the participant was unable to maintain CHR in the maintenance schedule.; Taken by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML. For the first cycle of therapy only, imatinib was started on Day 4 of homoharringtonine treatment.
Intervention MeSH terms: Imatinib Mesylate; Homoharringtonine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: ChemGenex Pharmaceuticals, Ltd; ChemGenex Pharmaceuticals; ChemGenex; Chronic Myeloid Leukemia; Myeloid Leukemia, Chronic; Leukemia; Myeloid Leukemia; Chronic Phase; Accelerated Phase; Blast Phase; Myeloid, Leukemia, Chronic, Accelerated Phase; Myeloid, Leukemia, Chronic; Leukemia, Myeloid, Chronic; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Chronic Phase; Leukemia, Myeloid, Accelerated-Phase; Myeloid, Leukemia, Chronic, Chronic Phase; Leukemia, Myeloid, Accelerated Phase; Homoharringtonine; Omacetaxine

Summary:

      This will be an open label, multi-center study of up to 77 patients with CML in chronic,
      accelerated or blast phase who have developed resistance to or have failed previous treatment
      with Gleevec (imatinib mesylate). Because these patients may still be sensitive to Gleevec,
      adding Homoharringtonine may restore a response to Gleevec or the combined treatment may
      promote a better response than using Gleevec alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients 16 years or older

          -  Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in either
             chronic, accelerated or blast phase

          -  Patients with chronic phase CML will be either refractory (failed to achieve
             hematologic or cytogenetic response) or resistant (responded initially but
             subsequently lost hematologic or cytogenetic response) to prior imatinib mesylate
             therapy. Failure to achieve cytogenetic response is defined as follows: no cytogenetic
             response after 3 months of therapy with imatinib mesylate, no major cytogenetic
             response at 12 months of therapy, loss of complete cytogenetic response documented
             twice, or loss of major cytogenetic response at least once.

          -  Patients with accelerated or blast phase may be newly diagnosed and previously
             untreated or if previously treated with imatinib mesylate, will be refractory or
             resistant to this agent or have failed to achieve at least a complete hematologic or
             cytogenetic response to treatment, as previously defined.

          -  Patients in accelerated phase will meet one or more of the following criteria: greater
             than or equal to 15% through less than 30% blasts in peripheral blood or bone marrow,
             greater than or equal to 30% blasts + promyelocytes in peripheral blood or bone
             marrow, greater than or equal to 20% basophils in peripheral blood, platelet count
             less than 100*10^9/L unrelated to therapy or clonal evolution.

          -  CML in blast phase will be defined as greater than or equal to 30% blasts in the bone
             marrow or presence of extramedullary disease

          -  Patients must have completed all previous anti-leukemic therapy for at least 2 weeks,
             except as noted, and have fully recovered from side effects of a previous therapy,
             unless disease progression necessitates early therapy. Patients may receive
             leukapheresis, hydroxyurea and anagrelide for up to 24 hours prior to start of study
             treatment. Patients receiving imatinib mesylate may continue to receive it
             uninterrupted, except for a 3-day window at treatment cycle 1.

          -  Bilirubin less than or equal to 2 times the upper limit of normal (ULN); alanine
             aminotransferase (ALT) less than or equal to 3 times ULN; creatinine less than or
             equal to 1.5 times ULN

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

          -  Be able to comply with the requirements of the entire study

          -  Be able and willing to provide written informed consent prior to any study related
             procedure

          -  Patients and their partners must use an effective contraceptive during the study
             dosing period. The following are considered effective contraceptives: oral
             contraceptive pill, condom, diaphragm plus spermicide, abstinence, patient or partner
             surgically sterile, patient or partner more than 2 years post-menopausal, or
             injectable or implantable agent/device.

        Exclusion Criteria:

          -  New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or
             any other uncontrolled cardiac condition such as angina pectoris, clinically
             significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or
             congestive heart failure

          -  Myocardial infarction in the previous 12 weeks

          -  Other intercurrent illness which would preclude study conduct and assessment,
             including but not limited to another active malignancy, uncontrolled and active
             infection, positive human immunodeficiency virus (HIV) or human T-cell lymphotropic
             virus (HTLV) I/II status

          -  Pregnant or lactating

          -  Any medical or psychiatric condition which may compromise the ability to give written
             informed consent or to comply with the study protocol