mercaptopurine

P1/2, N=18, Completed, Kristoffer Rohrberg | Recruiting --> Completed | N=39 --> 18

Thiopurines such as 6-mercaptopurine (6-MP) are central to maintenance therapy for pediatric acute lymphoblastic leukemia (ALL), yet their narrow therapeutic index frequently causes dose-limiting myelosuppression in genetically susceptible patients...Its affordability and minimal infrastructure requirements make it suitable for integration into routine pre-treatment workflows in India, enabling genotype-guided thiopurine dosing and reducing the risk of treatment-related toxicity. This assay supports a scalable path toward equitable implementation of pharmacogenomics in resource-limited pediatric oncology settings.

P1/2, N=276, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) induction achieved morphological complete remission, but measurable residual disease (MRD) persisted. Consolidation with mini-cyclophosphamide, vincristine, and dexamethasone (mini-CVD) and prednisone, vincristine, methotrexate, and 6-mercaptopurine (POMP) maintenance failed to eradicate MRD, and overt relapse occurred at month 7. Nelarabine salvage was initiated...Early molecular risk stratification and deployment of targeted agents, venetoclax-based combinations, or timely allogeneic transplantation should be considered before irreversible genomic complexity emerges. Prospective studies tailored to high-risk cytogenetic subsets of MPAL are urgently needed.

Multivariate analysis was performed, and the dosage was adjusted for age, sex, and mercaptopurine...Preemptive NUDT15 genotyping did not significantly reduce febrile neutropenia episodes in our cohort of pediatric patients with ALL, although it allowed a potential reduction in HR patients. Clinicians should consider preemptive testing, particularly in HR and VHR patient groups, to optimize ALL treatments and reduce adverse events.

The current guideline describes the gene-drug interactions for TPMT, NUDT15 and thiopurines (azathioprine, 6-mercaptopurine and thioguanine). For TPMT or NUDT15 IM treated for leukaemia, starting with the normal dose can be considered and then decrease the dose to the advised dose described above in case toxicities occur. For NUDT15 PM reduced starting dose is advised only if an alternative is not possible, due to a higher uncertainty in the calculated dose reduction for NUDT15 PM than for TPMT PM.DPWG classifies genotyping for TPMT and NUDT15 "essential" before thiopurine initiation.

P2, N=355, Completed, Abivax S.A. | Phase classification: P2b --> P2 | N=254 --> 355

The thiopurines 6-mercaptopurine and 6-thioguanine (TG) are analogs of guanine and are used in the treatment of hematological malignancies and immune-mediated inflammatory diseases. dMeTG could also be detected in patient samples, although in low amounts and primarily in samples with high DNA-TG levels. The developed method for the quantitation of dMeTG and dTG can be used in further studies to investigate the role of DNA-MeTG in the mechanism of action of thiopurines, including its antileukemic efficacy and effects on acquired mutations.

Excessive 6-thioguanine (6-TGN) levels worsen neutropenia, while elevated 6-methylmercaptopurine (6-MMP) levels contribute to hepatotoxicity. In contrast, two variants in the IMPDH1 gene, rs2228075 and rs2278294, are correlated with more frequent neutropenia. These findings highlight novel genetic variants influencing 6-MP metabolism and toxicity in paediatric ALL patients.

HOXA5 plays a dual role in solid versus hematologic malignancies and serves as a key spatial immune regulator. It is a robust prognostic biomarker and therapeutic target in AML, with mercaptopurine representing a promising repurposing candidate.

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

P2, N=53, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Apr 2028 --> Mar 2029 | Trial primary completion date: Apr 2028 --> Mar 2029