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

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01148134
• Other study ID #: 10-0300-CE
• Status: Terminated
• Phase: N/A
• First received: June 18, 2010
• Last updated: January 10, 2013
• Start date: June 2010
• Est. completion date: April 2012

Study information

• Verified date: January 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes