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

NCT ID: NCT01906671

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2018-11-30

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.

Conditions

Acute Lymphoblastic Leukemia; 6-mercaptopurine Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Puri-Nethol

Tablet formulation of 6-mercaptopurine

Group Type: EXPERIMENTAL

Xaluprine

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Xaluprine

Oral liquid formulation of 6-mercaptopurine

Group Type: EXPERIMENTAL

Xaluprine

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Cancer Society

OTHER

Sponsor Role: collaborator

Kjeld Schmiegelow

OTHER

Sponsor Role: lead

Responsible Party

Kjeld Schmiegelow

Professor in Pediatrics and Pediatric Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kjeld Schmiegelow, Professor

Role: PRINCIPAL_INVESTIGATOR

Pediatric Clinic II, Rigshospitalet, Copenhagen

Locations

Juliane Marie Centret, Rigshospitalet

Copenhagen, DK-, Denmark

Site Status: RECRUITING

Countries

Denmark

Facility Contacts

Kjeld Schmiegelow, Professor

Role: primary

kjeld.schmiegelow@regionh.dk

+45 35451357

Rikke Hebo Larsen, MD

Role: backup

rikke.hebo.larsen.01@regionh.dk

+45 35457932

References

Larsen RH, Hjalgrim LL, Grell K, Kristensen K, Pedersen LG, Brunner ED, Als-Nielsen B, Schmiegelow K, Nersting J. Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2020 Jul;86(1):25-32. doi: 10.1007/s00280-020-04097-x. Epub 2020 Jun 9.

Reference Type: DERIVED

PMID: 32519032 (View on PubMed)

Other Identifiers

2013-001236-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

6-MP formulation

Identifier Type: -

Identifier Source: org_study_id