A Phase III Study of Interferon-Refractory Patients With BCR/ABL(+) Chronic Myelogenous Leukemia (CML) Treated With Homoharringtonine (NSC #141633) vs. Hydroxyurea

Study start date: January 1, 2000

Documentation of Disease: 1.1 Diagnosis of Chronic Myelogenous Leukemia (CML) in chronic phase. Patients in either accelerated or blastic phases are not eligible. Clonal cytogenetic evolution alone does not exclude patients. See Appendix I for definitions of accelerated and blastic phases of CML. 1.2 Patients in whom a Philadelphia chromosome [t(9;22)] is not detectable by cytogenetic studies are eligible if they meet one of the following criteria: BCR/ABL protein detectable by immunoblotting BCR/ABL rearrangement detectable by Southern blot analysis Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL BCR/ABL translocation present by fluorescence in situ hybridization (FISH). Prior Treatment: 2.1 No previous therapy with homoharringtonine (HHT) 2.2 No more than six months cumulative (<180 days) of prior hydroxyurea (HU) therapy. However, patients may not have received more than 60 days of HU treatment after failing interferon. Patients with previous intolerance or failure to respond to HU are not eligible. 2.3 Patients must have failed an adequate trial (5M units/m2/day) of alpha-Interferon (IFN) or IFN/ara-C to be eligible, as defined below (any ONE of the following): Failure to achieve a complete hematologic response after 6 months of IFN therapy. Failure to achieve any cytogenetic response (i.e., still 100% Ph+) after 12 months of IFN therapy. Intolerable adverse effects of IFN therapy after at least one month of IFN treatment. Significant documented toxicity of ≥ grade 3 (using NCI Common Toxicity Criteria guidelines) due to IFN is required. Loss of a prior hematologic remission or cytogenetic response to IFN. A two-fold increase in WBC count when compared to WBC count when IFN therapy was initiated. Age ≥ 16 years Patients with uncontrolled tachyarrhythmias (such as, atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardias not adequately controlled) are not eligible. Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.