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NCT05811845

Mercaptopurine Therapeutic Drug Monitoring to Optimize the Maintenance Phase of Childhood ALL

Recruiting now Last updated 14 June 2024
What this trial tests

trial in Acute Lymphoblastic Leukemia in 250 participants. Currently enrolling.

Timeline
30 July 2022
Primary endpoint
30 July 2025
31 December 2026

Quick facts

Lead sponsorIRCCS Burlo Garofolo
StatusRecruiting now
Study typeOBSERVATIONAL
Enrollment250
Start date30 July 2022
Primary completion30 July 2025
Estimated completion31 December 2026
Sites4 locations across Italy

Conditions studied

Sponsor

IRCCS Burlo Garofolo — full company profile →

Who can join

Under 18, any sex, with Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in children (\<18 years). The success of pediatric ALL therapy is remarkable but important challenges still need to be faced, including cure rates in specific patients' subsets (e.g.: adolescents and relapsed patients), and short- and long-term chemotherapy-related toxicities. The therapeutic scheme of the Associazione Italiana Emato-oncologia pediatrica (AIEOP) ALL protocols consists in a more intensive and toxic earlier phase (to induce and consolidate remission, about 6 months), followed by a prolonged period of immunosuppression (achieved by self- or parent-administered daily mercaptopurine (MP) and weekly methotrexate (MTX) per os). It is now well established that the length of the maintenance phase (up to 24 months after diagnosis) is as necessary as the early remission induction for sustained event-free survival (EFS). Both MP and MTX can lead to potentially serious complications, including potentially life-threatening myelosuppression and infections. To exert its therapeutic effect, MP requires an intracellular enzymatic conversion into active thionucleotides (TGN) and is thus susceptible to intra- and inter-individual variations in efficacy and toxicity. Patients carrying variants in TPMT and NUTD15 genes are at risk of adverse effects when treated with standard MP doses: these patients are identifiable by pre-emptive genotyping. Recent studies demonstrated that an adequate and constant MP exposure during maintenance is associated with higher therapeutic success. Prescribed MP doses are often changed by physicians to target a white blood cell count (WBC) range of 2.0-3.0 × 109/L during maintenance. In the AIEOP ALL 2009 protocol, patients with lower mean TGN exposure during maintenance showed a trend towards a higher risk of relapse compared to others. Similarly, patients with higher intra-individual variability in TGN over time showed a trend towards a worse outcome. Daily compliance to prescribed MP over time is a challenging issue for patients and may result in less effective therapy. The high intra-individual variability in exposure due to the frequent dose adjustments and the potential lack of patients' adherence to oral MP therapy over time might contribute to the risk of relapse. The aim of this study is to assess through therapeutic drug monitoring of MP if patients' exposure during maintenance is adequate and constant.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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Other recruiting trials for Acute Lymphoblastic Leukemia

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Data sources for this page

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