Clinical trial NCT01148134: 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
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 type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Acute Lymphoblastic Leukemia
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2010-06-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Acute Lymphoblastic Leukemia will be selected from the Leukemia Clinic at Princess Margaret Hospital.

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.


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 18-24 months
Secondary outcomes:
measure: 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.
timeFrame: 18-24 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Joseph M Brandwein, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: