A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy
- Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting
≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib
mesylate or c-ABL therapy.
- Explore the safety profile of this drug in these patients.
- Explore the pharmacokinetic profile of this drug and its N-oxide metabolite PHA-816359
- Explore the modulation of histone H3 and CRKL phosphorylation after PHA-739358
- Explore the relationship between plasma drug levels and the modulation of histone H3
and CRKL phosphorylation.
- Explore the clinical efficacy of this drug, in terms of cytogenetic response in bone
- Explore response depending on status of T315I mutation in BCR-ABL kinase.
OUTLINE: This is a pilot, open-label, multicenter study.
Patients receive PHA-739358 IV over 6 hours on days 1, 8, and 15. Treatment repeats every 28
days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients
benefitting from treatment may receive additional courses at the discretion of the
Patients undergo blood collection and bone marrow biopsies periodically for pharmacologic
and biomarker correlative studies.
After completion of study treatment, patients are followed every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 16 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase
Ronald Paquette, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|