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

Terminated

• Conditions: Acute Lymphoblastic Leukemia

• Registration Number: NCT01148134
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-18
• Study First Submitted QC: 2010-06-18
• Study First Posted: 2010-06-22
• Primary Completion: 2012-04
• Study Completion: 2012-04
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-10
• Last Update Posted: 2013-01-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	18-24 months

Secondary Outcome Measures

Name	Time	Method
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.	18-24 months

Trial Locations

Locations (1)

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada