FLT3 I836

We also examined the effects of I836 variants on binding affinity to sorafenib using molecular docking...Many single-nucleotide variations in FLT3 have an impact on its structure and function. Thus, the annotation of FLT3 SNVs and the prediction of their deleterious pathogenic impact will facilitate an insight into the tumorigenesis process and guide experimental studies and clinical implications.

P1, N=50, Recruiting, Oryzon Genomics S.A. | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=33, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting

Detectable persistence of FLT3-TKD variants in blood from AML patients in first remission prior to first alloHCT is rare, but at a VAF level of 0.1% was strongly associated with increased relapse and death after transplant compared to those testing negative. In contrast to FLT3-ITD NGS-MRD, no evidence was found to support lowering the NGS-MRD VAF threshold from 0.1% to 0.01% for FLT3-TKD. Alternative methodology may further improve NGS-MRD test performance.

P2, N=33, Not yet recruiting, French Innovative Leukemia Organisation

P3, N=371, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Jul 2023 --> Jul 2024

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Trial completion date: Nov 2025 --> Mar 2026 | Trial primary completion date: Nov 2025 --> Feb 2024

A class of drugs, tyrosine-kinase inhibitors (TKI), targeting mutated FLT3, is already available with 1 and 2 generation molecules, but only midostaurin and gilteritinib are currently approved...Indeed, FLT3 inhibitors have significantly contributed to reducing the negative impact of FLT3 mutations on the prognosis of AML patients who are no longer considered at high risk by the European LeukemiaNet (ELN) 2022. Finally, several ongoing efforts to overcome resistance to FLT3-inhibitors will be presented: new generation FLT3 inhibitors in monotherapy or combined with standard chemotherapy, hypomethylating drugs, or IDH1/2 inhibitors, Bcl2 inhibitors; novel anti-human FLT3 monoclonal antibodies (e.g., FLT3/CD3 bispecific antibodies); FLT3-CAR T-cells; CDK4/6 kinase inhibitor (e.g., palbociclib).

P3, N=183, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2023 --> Jun 2024

P3, N=511, Completed, Novartis Pharmaceuticals | Terminated --> Completed

P3, N=183, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial primary completion date: Dec 2023 --> Mar 2023

P1/2, N=70, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Apr 2028 --> Jul 2028 | Trial primary completion date: Apr 2028 --> Jul 2028

P3, N=183, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial primary completion date: Jan 2023 --> Dec 2023

P3, N=183, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2023 --> Dec 2023

P1, N=50, Recruiting, Oryzon Genomics S.A. | Not yet recruiting --> Recruiting

Posttransplant survival was similar across the two study arms in ADMIRAL, but higher remission rates with gilteritinib facilitated receipt of HSCT. Gilteritinib as posttransplant maintenance therapy had a stable safety and tolerability profile and was associated with low relapse rates. Taken together, these data support a preference for bridging therapy with gilteritinib over chemotherapy in transplant-eligible patients.

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Trial completion date: Oct 2022 --> Nov 2025 | Trial primary completion date: Oct 2022 --> Nov 2025

P1/2, N=70, Recruiting, Astellas Pharma Global Development, Inc. | Not yet recruiting --> Recruiting

P1, N=50, Not yet recruiting, Oryzon Genomics S.A.

P1/2, N=70, Not yet recruiting, Astellas Pharma Global Development, Inc.

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Trial primary completion date: Jul 2022 --> Oct 2022

P1b, N=0, Withdrawn, City of Hope Medical Center | N=36 --> 0 | Not yet recruiting --> Withdrawn

P3, N=371, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Feb 2022 --> Jul 2023

In recent years the US Food and Drug Administration (FDA) has been very active in approving targeted therapeutic drugs for AML patients including Midostaurin (Rydapt; 2017) and Gilteritinib (Xospata;2018) for FLT3 mutations; Enasidenib (Idhifa; 2017) for IDH2 mutations and Ivosidenib (Tibsovo; 2018) for IDH1 mutations. The IDH1 CDx, IDH2 CDx and FLT3 CDx tests are highly sensitive and Versiti provides average turn around time of 3 business days which enable rapid decision making on the recently available drug therapies for AML patients. We strongly recommend that the IDH1 CDx, IDH2 CDx and FLT3 CDx tests should be performed on all AML patients for better care.

P3, N=511, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was analyzed to be futile hence was stopped after Futility Analysis.

P1b, N=36, Not yet recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Dec 2023 | Initiation date: Feb 2021 --> Oct 2021 | Trial primary completion date: Dec 2022 --> Dec 2023

P3, N=511, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> Feb 2021 | Trial primary completion date: Dec 2021 --> Jan 2021

Subsequently the patient underwent three consolidation cycles with HD Ara-C and midostaurin (days 8-21). It is important to note that the patient had remained free from leukaemia during three decades and a half, with AML developing only after acquisition of two other gene mutations (NPM1 and FLT3 TKD). These observations shed light on the paradigm of multiple genetic hits hypothesis of leukemogenesis and, after demonstration of the same IDH1 (R132H) mutation in chondroma tissue, prompt us to monitor the patient rather than candidate him to alloHCT in I CR.

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Trial completion date: Jul 2021 --> Oct 2022 | Trial primary completion date: Apr 2021 --> Jul 2022

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Recruiting --> Active, not recruiting

P3, N=512, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2021 --> Dec 2021 | Trial primary completion date: Jan 2021 --> Dec 2021

P3, N=371, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Feb 2021 --> Dec 2021

P3, N=146, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting | N=250 --> 146

P1b, N=36, Not yet recruiting, City of Hope Medical Center

P3, N=250, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2021 --> Aug 2023 | Trial primary completion date: Apr 2021 --> Dec 2022

P3, N=510, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> Dec 2020 | Trial primary completion date: Oct 2019 --> Dec 2020

P3, N=318, Recruiting, Astellas Pharma Inc | Trial completion date: Jun 2020 --> Jul 2021 | Trial primary completion date: Mar 2020 --> Apr 2021