No registrations found.
ID
Source
Brief title
Health condition
ALL, children, vincristine, azole therapy, pharmacokinetics
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic data of vincristine and the active metabolite M1 in peripheral blood.
Secondary outcome
1. Serum levels of azoles;
2. Vincristine toxicity will be assessed.
Background summary
Vincristine (VCR) is an important component in the treatment of acute lymphoblastic leukemia (ALL) in children. Proper dosing of vincristine is required to maximize disease control while avoiding toxicity. Peripheral and autonomic neuropathies are the most common side effects which can be life-threatening. Vincristine pharmacokinetics are time- and dose-dependent and considerable intra- and interpatient variation have previously been reported. Vincristine is predominantly metabolized in the liver by the cytochrome P450 (CYP) 3A family of enzymes and eliminated by an efflux pump, P-glycoprotein (P-gp). Inhibition of CYP3A4 by several drugs, such as azole antifungals, could increase vincristine exposure and potentiate the side effects caused by vincristine. Since in paediatric oncology patients azoles are increasingly being used for prophylaxis and treatment of fungal infections, guidelines for the co-administration of vincristine and azole therapy are necessary. The azoles used for antifungal prophylaxis are itraconazole, voriconazole and fluconazole. Several case reports suggest that co-administration of azoles and vincristine lead to increased toxicity, but this has not been studied specifically. It is not known whether these side-effects are related to a higher exposure of vincristine, and to what extent this exposure is increased. Information of the increase in plasma levels of vincristine during concomitant azole therapy may lead to evidence-based dosing guidelines for the effective and safe co-administration of these drugs, assuming that lower dose-levels of vincristine are needed.
Study objective
The aim of this study is to provide evidence based dosing guidelines for vincristine in combination with azoles. Therefore we will study the pharmacokinetics of vincristine with and without concomitant azole therapy in pediatric patients with acute lymphoblastic leukemia.
Study design
Sampling will be performed around 2 VCR administrations during induction and intensification phase of the standard treatment of ALL (DCOG-ALL-10 protocol).
Toxicity will be assessed during 4 weeks following the last sampling.
Intervention
No intervention, observation of blood levels of vincristine.
N.K.A. Eijkelenburg, van
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5663050
n.k.vaneijkelenburg@amc.nl
N.K.A. Eijkelenburg, van
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5663050
n.k.vaneijkelenburg@amc.nl
Inclusion criteria
1. Diagnosed with acute lymphoblastic leukemia;
2. Treatment according to DCOG ALL-10-protocol, induction phase and intensification phase for Medium Risk Group patients;
3. Vincristine 1.5 mg/m2 or 2 mg/m2 as iv bolus;
4. Age 1 - < 18 years;
5. Azole group: Azole therapy started at least 5 days before planned VCR treatment (7 days for fluconazole);
6. Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.
Exclusion criteria
1. Blood sampling not possible;
2. Patient refusal or parent refusal;
3. Not able to comply with scheduled follow-up;
4. Patients with underlying neurological disease such as Charcot-Marie-Tooth disease or Guillain-Barre syndrome;
5. Patients with underlying Down syndrome.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL2739 |
| NTR-old | NTR2877 |
| Other | ABR : 36660 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |