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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001236-21 | EudraCT Number |
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| Name | Class |
|---|---|
| Danish Cancer Society | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Puri-Nethol | Experimental | Tablet formulation of 6-mercaptopurine |
|
| Xaluprine | Experimental | Oral liquid formulation of 6-mercaptopurine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xaluprine | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to maximum concentration (Tmax) | Time to maximum concentration (Tmax) | Will be measured within a six months after collection of the blood samples |
| Measure | Description | Time Frame |
|---|---|---|
| Area under curve(AUC) | Area under curve(AUC) | Will be measured within six months after collection of the blood samples |
| Maximum concentration (Cmax) | Maximum concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kjeld Schmiegelow, Professor | Pediatric Clinic II, Rigshospitalet, Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Juliane Marie Centret, Rigshospitalet | Recruiting | Copenhagen | DK- | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32519032 | Derived | 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. |
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| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D015122 | Mercaptopurine |
| ID | Term |
|---|---|
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011687 | Purines |
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| Puri-Nethol | 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. |
|
| Will be measured within six months after collection of the blood samples |
| Time to half-life (T½) | Time to half-life (T½) | Will be measured within six months after collection of the blood samples |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |