This trial is active, not recruiting.

Condition leukemia
Treatments danusertib, laboratory biomarker analysis, pharmacological study
Phase phase 2
Sponsor Jonsson Comprehensive Cancer Center
Collaborator National Cancer Institute (NCI)
Start date March 2007
End date December 2009
Trial size 16 participants
Trial identifier NCT00335868, CDR0000486219, NERVIANO-AURA-6202-005, UCLA-0601009-01


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Masking open label
Primary purpose treatment

Primary Outcomes

Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase
time frame:
Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities
time frame:
Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing
time frame:
Changes in histone H3 and CRKL phosphorylation
time frame:
Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response
time frame:
Complete, partial, or minor cytogenetic response in bone marrow
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy
Description OBJECTIVES: - 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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).