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Report for Clinical Trial NCT03690115

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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."

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

NCT03690115 Leukemia, Myeloid, Acute
MeSH:Leukemia, Myeloid Leukemia, Myeloid, Acute
HPO:Acute megakaryocytic leukemia Acute myeloid leukemia Myeloid leukemia

1 Interventions

Name: Ponatinib 30 MG

Description: Administration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient
Type: Drug
Group Labels: 1

Experimental


Primary Outcomes

Measure: Relapse incidence at 2 years from transplant

Time: 2 years

Secondary Outcomes

Description: time interval from the graft (day 0) until the date of last follow-up or death

Measure: Overall survival

Time: 2 years

Description: time interval from the date of the graft (day 0) until the date of last follow-up, death or relapse

Measure: Leukemia free survival

Time: 2 years

Description: incidence of mortality due to all causes except relapse after transplant, considering that cause of death for patients having relapsed but dying from another cause is relapse

Measure: Non-relapse mortality (NRM)

Time: day 100

Description: NIH score

Measure: Acute and chronic GVHD

Time: 2 years

Description: an immunophenotype of PB lymphocytes will be performed by flow cytometry at +3, +6, +9 and +12 months post-transplant to study the reconstitutions of CD3, CD4 and CD8 T cells, B and NK cells. The results will be expressed as absolute counts (Giga/L). We want to establish the potential influence of ponatinib on the reconstitution of these cells

Measure: Influence of Ponatinib on Immune reconstitution PB lymphocyte cells

Time: 1 years

Description: Donor peripheral blood and CD3 T cells chimerism will be studied using molecular markers and RT-PCR at day +30, +60, +90, and +6, +12 months post-transplant. We want to establish the potential influence of ponatinib on the chimerism post-transplant.

Measure: Inflence of Ponatinib on Chimerism of Donor peripheral blood and CD3 T cells

Time: 1 years

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Time: 2 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 T315I

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. --- T315I ---



HPO Nodes


HPO:
Protein Mutations 0
SNP 0