NCT03690115

Study of Ponatinib (Iclusig) for Prevention of Relapse After Allogeneic Stem Cell Transplantation (allo-SCT) in FLT3-ITD AML Patients

Phase 2 Study of Ponatinib (Iclusig) for Prevention of Relapse After Allogeneic Stem Cell Transplantation (allo-SCT) in FLT3-ITD AML Patients: the PONALLO Trial."

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Versailles Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Recent advances in acute myeloid leukemia (AML) have been characterized by a better understanding of disease biology. As such, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have been recognized as conferring a poor prognosis. The FLT3-ITD molecular mutation is observed in about one-quarter of patients diagnosed with AML. Patients presenting with this abnormality are referred for early allogeneic stem-cell transplantation (allo-SCT). However, some data suggest that FLT3-ITD remains associated with a poor prognosis even after allo-SCT because of higher risk of relapse and strategies for preventing relapse in the post-transplant setting are required (Hu et al, Expert Rev Hematol, 2014). For example, in a large cohort of patients (Brunet et al, JCO, 2012), the incidence of relapse for FLT3-ITD AML patients after allo-SCT was 30% at 2-years, significantly higher compared to FLT3-ITD negative patients (p=0.006). Ponatinib (Iclusig®) is an orally available, tyrosine kinase inhibitor with a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. Ponatinib also has in vitro inhibitory activity against a discrete set of kinases implicated in the pathogenesis of other hematologic malignancies, including FLT3, KIT, fibroblast growth factor receptor 1 (FGFR1), and platelet derived growth factor receptor α (PDGFRα). In vitro activity of ponatinib in AML has been already demonstrated (Gozgit et al, Mol Cancer Ther, 2011; Smith et al, Blood 2013). If some trials are on-going to test ponatinib alone or in combination with chemotherapy in FLT3-ITD AML (Clinical.trials.gov), no study is dedicated to the use of ponatinib in the post-transplant setting in order to prevent relapse in these patients. The main goal of this study will be to determine the maximal tolerated dose (MDT) of ponatinib after allo-SCT in FLT3-ITD AML patients, then to investigate the efficacy of ponatinib in a larger cohort of patients

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Ponatinib 30 MG	Administration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient

Timeline

• Start date: 2019-12-02
• Primary completion: 2023-12-05
• Completion: 2024-12-31
• First posted: 2018-10-01
• Last updated: 2025-03-25

Locations

14 sites across 1 country: France