PHA-739358 in Treating Patients With Chronic Myelogenous Leukemia That Relapsed After Imatinib Mesylate or c-ABL Therapy
|ClinicalTrials.gov Identifier: NCT00335868|
Recruitment Status : Unknown
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was: Active, not recruiting
First Posted : June 12, 2006
Last Update Posted : December 18, 2013
RATIONALE: PHA-739358 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well PHA-739358 works in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Drug: danusertib Other: laboratory biomarker analysis Other: pharmacological study||Phase 2|
- 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 in plasma.
- Explore the modulation of histone H3 and CRKL phosphorylation after PHA-739358 administration.
- 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 marrow.
- 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 investigator.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy|
|Study Start Date :||March 2007|
|Estimated Primary Completion Date :||December 2009|
- Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase
- Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities
- Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing
- Changes in histone H3 and CRKL phosphorylation
- Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response
- Complete, partial, or minor cytogenetic response in bone marrow
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00335868
|United States, California|
|Jonsson Comprehensive Cancer Center at UCLA|
|Los Angeles, California, United States, 90095-1781|
|Study Chair:||Ronald Paquette, MD||Jonsson Comprehensive Cancer Center|