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

This study has been terminated.
(Analysis of the first 10 patients did not show anyt trend toward differences in PK profiles between imatinib vs no imatinib groups.)
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01148134
First received: June 18, 2010
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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
Acute Lymphoblastic Leukemia

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 10
Study Start Date: June 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Bcr-Abl positive ALL
Bcr-Abl negative ALL

  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 with Acute Lymphoblastic Leukemia will be selected from the Leukemia Clinic at Princess Margaret Hospital.

Criteria

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.
  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: NCT01148134

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

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01148134     History of Changes
Other Study ID Numbers: 10-0300-CE
Study First Received: June 18, 2010
Last Updated: January 10, 2013
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Vincristine
Imatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014