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

NCT05811845 | Recruiting

• 1 other identifier: 57/22
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia; Compliance; Mercaptopurine

Outcome Measures

Primary Outcomes (4)

• To establish the variability of MP systemic exposure (TGN) over time

  MP metabolites will be evaluated in erythrocytes of peripheral blood according to standardized methods

  After 18 months from the start of treatment

• To establish the correlation between MP systemic exposure (TGN) and absolute neutrophil count to identify the ideal TGN therapeutic range

  MP metabolites will be evaluated in erythrocytes of peripheral blood according to standardized methods

  After 18 months from the start of treatment

• To establish if TGN levels and intra-individual variability (TGN-CV) could monitor patients' adherence during the long-term maintenance phase

  MP metabolites will be evaluated in erythrocytes of peripheral blood according to standardized methods

  After 18 months from the start of treatment

• To determine the impact of TGN on EFS

  MP metabolites will be evaluated in erythrocytes of peripheral blood according to standardized methods

  After 18 months from the start of treatment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with new diagnosis of ALL

You may qualify if:

• Newly diagnosed ALL
• Age \<18 years at diagnosis
• Written informed consent given

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (4)

Fondazione MBBM / A.O. San Gerardo

Monza, Monza Brianza, Italy

RECRUITING

IRCCS Ospedale Pediatrico "Bambino Gesù"

Roma, Italy

RECRUITING

Presidio Infantile Regina Margherita

Torino, Italy

RECRUITING

IRCCS materno infantile Burlo Garofolo

Trieste, 34137, Italy

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Patient Compliance

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Marco Rabusin, MD

  IRCCS materno infantile Burlo Garofolo

  STUDY DIRECTOR

Central Study Contacts

Marco Rabusin, MD

CONTACT

+390403785111; marco.rabusin@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: April 13, 2023
• Study Start: July 30, 2022
• Primary Completion: July 30, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)