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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01906671
• Other study ID #: 6-MP formulation
• Secondary ID: 2013-001236-21
• Status: Recruiting
• Phase: Phase 4
• First received: July 16, 2013
• Last updated: April 19, 2018
• Start date: June 2013
• Est. completion date: November 2018

Study information

• Verified date: April 2018
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: November 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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:

Related Conditions & MeSH terms

• 6-mercaptopurine Therapy
• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Xaluprine
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
• Puri-Nethol
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.

Locations

Country	Name	City	State
Denmark	Juliane Marie Centret, Rigshospitalet	Copenhagen	DK-

Sponsors (2)

Lead Sponsor	Collaborator
Kjeld Schmiegelow	Danish Cancer Society

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to maximum concentration (Tmax)	Time to maximum concentration (Tmax)	Will be measured within a six months after collection of the blood samples
Secondary	Area under curve(AUC)	Area under curve(AUC)	Will be measured within six months after collection of the blood samples
Secondary	Maximum concentration (Cmax)	Maximum concentration (Cmax)	Will be measured within six months after collection of the blood samples
Secondary	Time to half-life (T½)	Time to half-life (T½)	Will be measured within six months after collection of the blood samples