Clinical trial NCT01215487: 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
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Myeloid Leukemia
Keywords: CML Predictive Study
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2010-10-06
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.

Hypothesis:

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.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of CML in chronic phase.
* ECOG \<2.
* Normal organ function and ULN Total bili, AST and ALT.
* Must have the ability to understand and sign a written consent form

Exclusion Criteria:

* Patients may not be receiving any other investigational agents.
* May not have prior treatment with Imatinib, Dasatinib, Nilotinib or other tyrosine kinase inhibitors.
* Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or nursing mothers
* Patients must have no prior malignancies except for; adequately treated non-melanoma skin cancer, cervical carcinoma-in-situ, adequately treated Stage I or II cancer from which the patient is in complete remission, or any other cancer from which the patient has been disease free for 5 years

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Leukemia BMT program of BC, Vancouver General Hospital, Hematology Research and Clinical Trials Unit
state: British Columbia
Study officials:
affiliation: University of British Columbia - Terry Fox Laboratory
name: Xiaoyan Jiang
role: STUDY_DIRECTOR
affiliation: University of British Columbia - Terry Fox Laboratory
name: Ryan Brinkman
role: STUDY_DIRECTOR
affiliation: University of British Columbia - Terry Fox Laboratory
name: Connie Eaves
role: STUDY_DIRECTOR
affiliation: University of British Columbia - St. Paul's Hospital Department of Hematology
name: Lynda Foltz
role: STUDY_DIRECTOR
References: