Pharmacokinetic Profile of Vincristine Administered With Imatinib for Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) Compared to That Without Imatinib for Bcr-Abl Negative ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01148134
Recruitment Status : Terminated (Analysis of the first 10 patients did not show anyt trend toward differences in PK profiles between imatinib vs no imatinib groups.)
First Posted : June 22, 2010
Last Update Posted : January 11, 2013
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

This study is characterizing the pharmacokinetics of vincristine using two different cohorts of patients. The first cohort includes patients with acute lymphoblastic leukemia (ALL) that are Bcr-Abl positive. This cohort of patients will receive vincristine along with imatinib in the induction chemotherapy regimen. The second cohort includes patients with ALL that are Bcr-Abl negative. This cohort of patients will receive vincristine without imatinib in the induction chemotherapy regimen. This study involves blood draws beginning on day 7 of the treatment protocol and these samples will be analyzed for pharmacokinetic parameters.

Imatinib and vincristine are both metabolized by the hepatic CYP 450 enzyme system. Imatinib is an inhibitor of the system and co-administration of imatinib and vincristine has the potential to increase the blood level of vincristine. This could explain the increased level of neurotoxicity that is currently being seen with the co-administration of these two agents in the treatment of Bcr-Abl positive ALL.

Condition or disease
Acute Lymphoblastic Leukemia

Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Pharmacokinetic Profile of Vincristine Administered Along With Imatinib in the Induction Chemotherapy of Bcr-Abl (Philadelphia Chromosome) Positive Acute Lymphoblastic Leukemia (ALL) Compared to That Without Imatinib in the Treatment of Bcr-Abl Negative ALL Patients
Study Start Date : June 2010
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Bcr-Abl positive ALL
Bcr-Abl negative ALL

Primary Outcome Measures :
  1. To characterize the pharmacokinetics of vincristine in two patient cohorts: Bcr-Abl positive ALL patients treated with the standard protocol with imatinib and Bcr-Abl negative ALL patients treated with the same protocol but without imatinib. [ Time Frame: 18-24 months ]

Secondary Outcome Measures :
  1. To determine if there are any objective differences in peripheral neuropathy and ileus between the two groups at Day 14, and to correlate these neurologic assessments with PK results. [ Time Frame: 18-24 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with Acute Lymphoblastic Leukemia will be selected from the Leukemia Clinic at Princess Margaret Hospital.

Inclusion Criteria:

  • Age >/= 18 years
  • New Diagnosis of Bcr-Abl positive ALL or Bcr-Abl negative ALL
  • Receiving induction chemotherapy with the standard Princess Margaret Hospital modified DFCI protocol
  • Will have a functioning central venous access catheter in-situ
  • Agreeing to participate in the study and sign the informed consent form

Exclusion Criteria:

  • Concomitant use of other agents that inhibit hepatic cytochrome CYP3A4, as these drugs may alter vincristine and imatinib levels
  • Elevated liver function tests: bilirubin >1.5xULN or AST/ALT >2.5xULN, or documented history of chronic liver disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01148134

Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Principal Investigator: Joseph M Brandwein, MD, FRCPC Princess Margaret Hospital, Canada

Responsible Party: University Health Network, Toronto Identifier: NCT01148134     History of Changes
Other Study ID Numbers: 10-0300-CE
First Posted: June 22, 2010    Key Record Dates
Last Update Posted: January 11, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Imatinib Mesylate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors