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

Sponsor

University of British Columbia (Other)

Overall Status

Completed

CT.gov ID

NCT01215487

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

116

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Procedure: Stem Cell and Mutational Assay

Study Design

Study Type:

Observational

Actual Enrollment :

68 participants

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

May 31, 2020

Actual Study Completion Date :

May 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leukemia BMT program of BC, Vancouver General Hospital, Hematology Research and Clinical Trials Unit	Vancouver	British Columbia	Canada	V5Z 1M9

Sponsors and Collaborators

University of British Columbia
Bristol-Myers Squibb

Investigators

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