This is a Phase I/II single site, open label clinical trial. The purpose of the Phase I portion is to determine the safety, tolerability, and recommended Phase II dose of Eicosapentaenoic Acid (EPA) when given in combination with a Tyrosine Kinase Inhibitor (TKI) in subjects with Chronic Myeloid Leukemia (CML) in chronic stable phase. The recommended Phase II dose will be the maximum tolerated dose (MTD) of EPA as determined by the evaluation of dose-limiting toxicities (DLTs). The Phase II portion will subsequently examine the Anti-CML effects of EPA when administered with a TKI at the recommended Phase II dose. This efficacy objective will be done by evaluating BCR-ABL p210 quantitative PCR blood levels every 3 months to 1 year.
Name: Eicosapentaenoic Acid
Description: Eicosapentaenoic Acid once per day orallyType: DrugEicosapentaenoic Acid (EPA)
Name: Tyrosine kinase inhibitor
Description: Tyrosine kinase inhibitor to be administered at subjects' pre-study doseType: DrugEicosapentaenoic Acid (EPA)
Description: Recommended Phase II dose of EPA will be established by using a standard 3 + 3 statistical design to determine the MTD as assessed by DLTs when administered orally in combination with a TKI in subjects with CML in stable chronic phase. Toxicity will be evaluated using the NCI Common Toxicity Criteria (CTC) version 5.0.
Measure: Phase I - Recommended Phase II dose of EPA Time: 1 monthDescription: BCR-ABL transcript levels will be assessed every 3 months post initiation of Eicosapentaenoic Acid to assess Anti-CML response.
Measure: Phase II - Anti-CML response to recommended Phase II dose Eicosapentaenoic Acid Time: 1 yearDescription: Using the NCI CTC Version 5.0, AEs will be assessed from the time of initiation of investigational medication
Measure: Number of subjects who experience treatment related Adverse Events (AEs) Time: 2 yearsDescription: Using the NCI CTC Version 5.0, the highest grade of all treatment related AEs collected will be used to determine severity
Measure: Severity of AEs experienced by study subjects Time: 2 yearsDescription: Proportion of protocol prescribed doses taken by subjects
Measure: Study subject compliance with investigational regimen Time: 2 yearsDescription: Log reduction from stable molecular response with bcr-abl PCR at MR 3 or more to bcr-abl to major molecular response (MR 4.5) or complete molecular response
Measure: Molecular responses of CML Time: 1 yearDescription: Analyzed by in vitro correlative studies using subject's plasma with effect on known leukemia cell line with CML leukemic stem cells.
Measure: Induction of apoptosis in CML leukemia stem cell by formation of Δ12-PGJ3 and other metabolites Time: 2 yearsSequential Assignment
There is one SNP
Known T315I mutation. --- T315I ---