A Study Investigating the Predictive Value of Philadelphia Positive Stem Cell Properties in Newly Diagnosed Patients With Chronic Myeloid Leukemia in Chronic Phase Receiving Treatment With Imatinib
Imatinib (IM) is first-line treatment for patients with newly diagnosed CML in chronic phase. The drug is associated with high rates of cytogenetic responses with minimal toxicity in approximately 80% of patients. In 20% of patients however, the disease is either initially unresponsive to IM (Imatinib), resistance develops within a few months, or blast crisis occurs early and unexpectedly following an initial response. An increasing body of clinical evidence indicates that single agent molecularly targeted therapy (as in Gleevec/Imatinib) will not cure most patients with CML, as molecular remissions are rare. There is currently no clinically useful predictive tests to identify AT DIAGNOSIS those patients who are destined to be IM failures. The authors of this study have recently demonstrated that CML stem/progenitor cells are biologically insensitive to IM and are also genetically unstable and rapidly generate IM-resistant mutants in vitro and in vivo. The team recently discovered that the CD34 stem/progenitor cells of newly diagnosed CML patients who subsequently fail to respond to IM treatment show a reduced response to IM and a higher frequency of BCR-ABL mutations by comparison of 14 IM non-responders with 11 IM-responders. If this finding can be validated in a larger prospective cohort of patients, this predictive test could be used to more rationally design treatment plans with early addition of alternative therapies ie: Dasatinib or combination therapies for patients according to their individual risk profiles.
The clinical response of newly diagnosed chronic phase CML patients to IM can be predicted by certain biological properties of their CD34 stem/progenitor cells which are variable among patients.
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||A Study Investigating the Predictive Value of Philadelphia Positive Stem Cell Properties in Newly Diagnosed Patients With Chronic Myeloid in Chronic Phase Receiving Treatment With Imatinib|
Specimens of whole blood will be collected, and used for measurement of sensitivity of the patient's individual pretreatment colony-forming cells (CFCs) to IM exposure in vitro, the level of expression of BCR-ABL, OCT1, ABCB1/MDR and ABCG2 transcripts in their CD34+ cells and the frequency of mutant BCR-ABL transcripts in the same cells. The cells are cultured for 3 weeks
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
1 - Chronic Myelogenous Leukemia Patients
Patients will be selected from patients referred to the primary hospital site for treatment and assessment. The patients will be approached by the physicians and or the study research nurse to consider participation in the study. Patients may be selected by participating off-site hospital centres and may be enrolled at those collaborating centres.
Procedure: Stem Cell and Mutational Assay
Laboratory blood testing
Please refer to this study by its ClinicalTrials.gov identifier: NCT01215487
|Contact: Xin Zhou||604 875-4111 ext firstname.lastname@example.org|
|Canada, British Columbia|
|Leukemia BMT program of BC, Vancouver General Hospital, Hematology Research and Clinical Trials Unit||Recruiting|
|Vancouver, British Columbia, Canada, V5Z 1M9|
|Study Director:||Xiaoyan Jiang||University of British Columbia - Terry Fox Laboratory|
|Study Director:||Ryan Brinkman||University of British Columbia - Terry Fox Laboratory|
|Study Director:||Connie Eaves||University of British Columbia - Terry Fox Laboratory|
|Study Director:||Lynda Foltz||University of British Columbia - St. Paul's Hospital Department of Hematology|