Clinical trial NCT01906671: Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
Official title: Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia
6-mercaptopurine Therapy
Keywords: 6-mercaptopurine
Drug formulation
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
First posted: 2013-07-24
Enrollment: 16
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time to maximum concentration (Tmax)
timeFrame: Will be measured within a six months after collection of the blood samples
Secondary outcomes:
measure: Area under curve(AUC)
timeFrame: Will be measured within six months after collection of the blood samples
measure: Maximum concentration (Cmax)
timeFrame: Will be measured within six months after collection of the blood samples
measure: Time to half-life (T½)
timeFrame: Will be measured within six months after collection of the blood samples
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Juliane Marie Centret, Rigshospitalet
state: DK-
Study officials:
affiliation: Pediatric Clinic II, Rigshospitalet, Copenhagen
name: Kjeld Schmiegelow, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.