Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of British Columbia
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01215487
First received: October 4, 2010
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

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 Intervention
Chronic Myeloid Leukemia
Procedure: Stem Cell and Mutational Assay

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Biospecimen Retention:   Samples With DNA

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


Estimated Enrollment: 250
Study Start Date: October 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01215487

Contacts
Contact: Xin Zhou 604 875-4111 ext 67290 xzhou@bccancer.bc.ca

Locations
Canada, British Columbia
Leukemia BMT program of BC, Vancouver General Hospital, Hematology Research and Clinical Trials Unit Recruiting
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
  More Information

Additional Information:
No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01215487     History of Changes
Other Study ID Numbers: H09-03255
Study First Received: October 4, 2010
Last Updated: September 18, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
CML Predictive Study

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 27, 2014