Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid

Phase 4

• Conditions: Acute Lymphoblastic Leukemia; 6-mercaptopurine Therapy
• Interventions: Drug: Xaluprine; Drug: Puri-Nethol

• Registration Number: NCT01906671
• Lead Sponsor: Kjeld Schmiegelow

Brief Summary

Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects.

In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem.

Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia.

The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-07-16
• Study First Submitted QC: 2013-07-23
• Study First Posted: 2013-07-24
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-19
• Last Update Posted: 2018-04-20
• Primary Completion: 2018-09
• Study Completion: 2018-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Childhood acute lymphoblastic leukemia patients, age 0-18 years at diagnosis, treated at the department of pediatrics and adolescent medicine, Rigshospitalet.
• Informed consent

Exclusion Criteria

• None

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Puri-Nethol	Xaluprine	Tablet formulation of 6-mercaptopurine
Puri-Nethol	Puri-Nethol	Tablet formulation of 6-mercaptopurine
Xaluprine	Xaluprine	Oral liquid formulation of 6-mercaptopurine
Xaluprine	Puri-Nethol	Oral liquid formulation of 6-mercaptopurine

Primary Outcome Measures

Name	Time	Method
Time to maximum concentration (Tmax)	Will be measured within a six months after collection of the blood samples	Time to maximum concentration (Tmax)

Secondary Outcome Measures

Name	Time	Method
Time to half-life (T½)	Will be measured within six months after collection of the blood samples	Time to half-life (T½)
Area under curve(AUC)	Will be measured within six months after collection of the blood samples	Area under curve(AUC)
Maximum concentration (Cmax)	Will be measured within six months after collection of the blood samples	Maximum concentration (Cmax)

Trial Locations

Locations (1)

Juliane Marie Centret, Rigshospitalet; 🇩🇰 Copenhagen, DK-, Denmark