Clinical Trial: Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase II Open-Label Study of the Intravenous Administration of Homoharringtonine (CGX-635) Combined With the Oral Administration of Gleevec in the Treatment of Patients With Chronic Myeloid Leukemia

Brief 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.

Detailed Summary: Every 4 weeks, the study medicine Homoharringtonine will be given by vein daily for 5 days along with continuing daily doses of the approved medicine Gleevec taken by mouth. The safety and effectiveness of this combined treatment in CML patients will be studied. Patients who do not achieve a meaningful hematologic or cytogenetic response after 4 cycles or less will be discontinued. Otherwise, patients may continue additional cycles of this combined treatment for a maximum of 12 cycles.
Sponsor: ChemGenex Pharmaceuticals

Current Primary Outcome:

  • Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [ Time Frame: up to month 4 ]

    Participants in accelerated or blast phase who converted to at least CML-chronic phase.

    CML in accelerated phase meets one or more of the following criteria: >=15% - <30% blasts in peripheral blood or bone marrow, >=30% blasts + promyelocytes in peripheral blood or bone marrow, >=20% basophils in peripheral blood; platelet count <100*10^9/L unrelated to therapy or clonal evolution. CML in blast phase have >=30% blasts in the bone marrow or presence of extramedullary disease.

    Meaningful responses include (in descending order of health)

    • Complete Hematologic Remission (CHR)
    • Partial Hematologic Remission (PHR)
    • Hematologic Improvement (HI)
    • Partial Response (PR)
    • Return to Chronic Phase (RCP). A return to chronic phase involves the disappearance of blastic phase features and a return to chronic phase CML picture, i.e., peripheral blasts <15%, peripheral blasts and promyelocytes <30%, peripheral basophils <20%, and platelets >100*10^9/L.
  • Proportion of Participants With Chronic Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [ Time Frame: up to month 4 ]

    Participants who are not in complete hematologic remission

    Original Primary Outcome:

    • Tolerance and toxicity of the combined Homoharringtonine and Gleevec treatment regimen
    • Proportion of patients with chronic phase CML who achieve complete hematologic remission (CHR) or improved cytogenetics if in CHR at study onset
    • Proportion of patients with accelerated or blast phase CML who convert to at least chronic phase CML


    Current Secondary Outcome: Participants With Complete Hematologic Remission Suppression of the Philadelphia Chromosome [ Time Frame: up to month 4 ]

    Complete hematologic remission was further classified according to the suppression of the Philadelphia chromosome (Ph) as:

    No cytogenetic response - Ph positive 100% Minimal cytogenetic response - Ph positive 35-90% Partial cytogenetic response - Ph positive 1-34% Complete cytogenetic response - Ph positive 0%



    Original Secondary Outcome:

    • Proportion of patients achieving hematologic improvement
    • Proportion of patients returning to chronic phase CML
    • Response rate of patients with extramedullary disease (EMD)
    • Proportion of patients with chronic, accelerated or blast phase CML, respectively, who achieve a hematologic response or cytogenetic response
    • Onset of response
    • Duration of response
    • Survival


    Information By: Teva Pharmaceutical Industries

    Dates:
    Date Received: June 20, 2005
    Date Started: October 2005
    Date Completion:
    Last Updated: January 8, 2015
    Last Verified: January 2015