A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy

- Chronic, accelerated, or blastic phase disease

- May have T315I mutation in BCR-ABL kinase

- Relapsed after prior imatinib mesylate or c-ABL therapy

- No CNS leukemia

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week)

- Transaminases ≤ 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Creatinine ≤ 1.5 times ULN

- No known history of HIV infection

- No active uncontrolled infection

- No grade 3 or 4 bleeding

- LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography

- No medical or psychiatric condition or laboratory abnormalities that would limit
study compliance or increase risk during study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 90 (female) or 180
(male) days after completion of study treatment

- No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable
angina) within the past 6 months

- No major thromboembolic event within the past 6 months, including any of the
following:

- Myocardial infarction

- Stroke

- Transient ischemic attack

- Pulmonary embolism

- Noncatheter-related deep-vein thrombosis

PRIOR CONCURRENT THERAPY:

- Recovered from all acute toxic effects (excluding alopecia) of prior therapy

- More than 2 weeks since prior chemoimmunotherapy

- Hydroxyurea must be discontinued 1 day prior to study therapy

- More than 4 weeks since prior major surgery

- No other concurrent approved or investigational anticancer treatment, including
chemotherapy, biologic response modifiers, hormones, or immunotherapy

- No other concurrent investigational drugs

- No concurrent participation in another treatment clinical trial