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A Study Investigating the Predictive Value of Intracellular and Plasma Imatinib Levels in Newly Diagnosed Patients With Chronic Myeloid Leukemia

18 Years
Not Enrolling
Chronic Myeloid Leukemia

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Trial Information

A Study Investigating the Predictive Value of Intracellular and Plasma Imatinib Levels in Newly Diagnosed Patients With Chronic Myeloid Leukemia

The use of imatinib for the treatment of chronic myeloid leukemia has significantly improved
the survival of most patients with this disease. This drug works by directly inhibiting the
cancer-causing protein BCR-ABL that is found inside the leukemia cells and therefore is the
first successful targeted treatment for cancer. Measuring the amount of the gene product for
BCR-ABL by very sensitive laboratory techniques as it decreases during therapy has been
extremely helpful in monitoring disease activity. Furthermore, in a subgroup of patients
whose leukemia cells decrease by more than a thousand-fold measured by this sensitive
technique during the first one or two years, these patients have a greater than 97% chance
that disease remains under excellent control for more than five years. Therefore,
discovering tests that would predict this marked decrease in BCR-ABL gene product at early
timepoints when any treatment changes could be done would be very useful. To study this, a
test that measures the amount of imatinib in a patient's bloodstream plasma has been
recently developed at a national reference laboratory, Warnex Medical Laboratories in Laval,
Quebec. Preliminary results from other national laboratories indicates that patients differ
in how much imatinib their bodies absorb and get into their bloodstream, and that patients
who absorb imatinib less well have a slightly lower chance of this thousand-fold reduction
in leukemia levels. However, because imatinib must get inside leukemia cells to inhibit
BCR-ABL, it likely that the amount of imatinib that is inside leukemia cells would predict
even better the response to the drug. Warnex Laboratories has recently developed a test that
can measure imatinib levels inside cells, and preliminary results indicate that patients
differ in how much imatinib gets inside their cells. Dr. Suzanne Kamel-Reid's laboratory at
Toronto General Hospital has also developed a test to measure the amount of gene product for
the pore that imatinib uses to enter leukemia and other blood cells (called h-OCT-1), and
her preliminary results also show that differs among patients. It is not clear if these
differences are due to differences in the leukemia cels themselves between patients, or in
differences between the way imatinib would get into any blood cells between patients.
Therefore we are undertaking this current study to see (1) which of the tests, or
combination of tests (bloodstream imatinib level, imatinib level inside cells, or h-OCT-1
level) best predicts how well patients patients respond to imatinib by the sensitive test
for BCR-ABL, and (2) whether the differences between patients in the level inside cells is
due specifically to the leukemia cells. In this trial, we will measure these levels on
patients who are about to begin treatment for their chronic myeloid leukemia with imatinib.
For practical purposes, participation in this trial would require patients to have extra
blood samples drawn at several visits when they would normally see their
hematologist/oncologist to monitor their disease and its treatment: within 28 days up to and
including Day 1 as long as collected prior to start of treatment with Imatinib, and once
Imatinib treatment is started, at 2 weeks, one month, 6 months , and 12 months. By obtaining
this information, we may better understand how to adjust imatinib therapy to achieve the
best response for more patients in the future. 

Inclusion Criteria:

- Patients must have a diagnosis of chronic myeloid leukemia in chronic phase (as
defined in Appendix A) within four weeks of study registration based on bone marrow
aspirate and peripheral blood counts. - Patients must have confirmation of the
Philadelphia chromosome or variants by cytogenetics, or FISH, or positive test for
bcr-abl by PCR. Patients with additional chromosomal abnormalities in addition to the
Philadelphia chromosome are eligible.

- Age >18 years.

- ECOG performance status <2. (Appendix B)

- Patients must have normal organ function as defined below:

- Total Bilirubin < 1.5 x Institutional Upper Limit of Normal (ULN)

- AST and/or ALT < 2.5 x Institutional Upper Limit of Normal (ULN)

- Eligibility of patients receiving any medications or substances known to affect or
determined following review of their case by the Principal Investigator.

Exclusion Criteria:

- Patients may not be receiving any other investigational agents.

- Patients may not have received prior treatment with Imatinib.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant or nursing women are excluded from this study because Imatinib has potential
teratogenic effects and excretion in breast milk is unknown.

- No prior malignancies except for: adequately treated non-melanoma skin cancer,
cervical carcinoma-in-situ, adequately treated Stage I or II cancer from which
patient is in complete remission, or any other cancer from which patient has been
disease free for 5 years.

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

To determine if intracellular levels of Imatinib in leukemic blood cells within two weeks of treatment initiation of patients with chronic myeloid leukemia in chronic phase predicts molecular and cytogenetic response at 6 and 12 months post treatment

Outcome Time Frame:

One year after starting therapy for chronic myeloid leukemia

Safety Issue:


Principal Investigator

Brian Leber, MDCM

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hamilton Health Sciences Corporation


Canada: Health Canada

Study ID:




Start Date:

July 2009

Completion Date:

April 2012

Related Keywords:

  • Chronic Myeloid Leukemia
  • CML
  • intracellular imatinib level
  • OCT-1
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive