Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML

• Percentage of Participants Achieving a Clinical Response by Subpopulation [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  Subpopulations reflect chronic myeloid leukemia (CML) phases: chronic, accelerated, and blast phase.
• Participants with Adverse Events by Subpopulation [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
  Subpopulations reflect chronic myeloid leukemia (CML) phases: chronic, accelerated, and blast phase.

• Time to Response [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  The time from the initiation of treatment until the date of first reported hematologic or cytogenetic response.
• Duration of Response [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  The time from the first reported date of hematologic or cytogenetic response, as defined above, until the earliest date of objective evidence of disease progression, relapse or death.
• Time to Disease Progression [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  The time from the initiation of treatment until the onset date of death, the development of accelerated-phase or blast-crisis CML, or the loss of complete hematologic or major cytogenetic response, whichever comes first.
• Overall Survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  The time from the initiation of treatment until death from any cause or the last day of patient contact or evaluation for patients that are lost to follow-up.
• Participants' Degree of Suppression of the Philadelphia Chromosome (Ph) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
• Participants' Degree of Suppression of BCR-ABL transcript levels [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
• Percentage of CML Participants with Accelerated or Blast Phase Who Return to Chronic Phase [ Time Frame: Up to four years ] [ Designated as safety issue: No ]
• Percentage of CML Participants with Accelerated or Blast Phase Who Show No Evidence of Leukemia [ Time Frame: up to four years ] [ Designated as safety issue: No ]
• Percentage of Participants with Extramedullary Disease (EMD) at Baseline Who Achieve a Clinical Response [ Time Frame: up to four years ] [ Designated as safety issue: No ]
• The Number of Induction Cycles to Achieve a Clinical Response [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]

• Degree of Hematologic Response
• Time to Response
• Time to progression
• Survival

A Phase II open-label trial of subcutaneous HHT (omacetaxine mepesuccinate) in the treatment of patients who are resistant to or intolerant to Tyrosine Kinase Inhibitors.

This will be an open label, multicenter study of subcutaneous HHT (omacetaxine mepesuccinate) therapy of patients with chronic myeloid leukemia (CML) in chronic, accelerated, or blast phase who have failed or are intolerant to tyrosine kinase inhibitor therapy. Patients will be treated with induction course cycles consisting of subcutaneous (SC) HHT 1.25 mg/m² twice daily for 14 consecutive days every 28 days. Patients will be evaluated every 7 days with complete blood and platelet counts while undergoing induction therapy; the number of consecutive doses of HHT or intervals between subsequent cycles may be adjusted, as clinically indicated, according to guidelines provided in the treatment plan.

Inclusion Criteria:

• Male or female patients, age 18 years or older
• Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
• Patients will have either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least two tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response).
• Acceptable Renal and Liver Function
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Sexually active patients and their partners must use an effective double barrier method of contraception

Exclusion Criteria:

• New York Heart Association classification (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
• Myocardial infarction in the previous 12 weeks.
• Other concurrent illness which would preclude study conduct and assessment
• uncontrolled and active infection, and positive HIV or positive HTLV I/II status, whether on treatment or not.
• 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.
• Lymphoid Ph+ blast crisis
• Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent

• Cephalon
• ChemGenex Pharmaceuticals