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

University Health Network, Toronto

Status: Terminated

Conditions: Acute Lymphoblastic Leukemia

Study type: Observational

Funder types: Other

Identifiers

NCT01148134

10-0300-CE

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

10 participants in 2 patient groups

Bcr-Abl positive ALL

Bcr-Abl negative ALL