AML, Adult Clinical Trial
Official title:
OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
Mutations in IDH genes are found in numerous cancers and more specifically in acute myeloid leukemia (AML). These mutations target specific amino acids, at positions 140 or 172 of IDH2, and 132 of IDH1. Mutant IDH proteins acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) into D-2 hydroxyglutarate (D-2HG), an oncometabolite which massively accumulates in IDH-mutated cells. At high levels, D-2HG behaves as a competitive inhibitor of αKG and affects the activity of Fe(II)/αKG-dependent dioxygenases. This enzymatic family is involved in a broad spectrum of pathways such as demethylation of histone (JHDM histone demethylases) or DNA (methylcytosine hydroxylases of the TET family). As a result, IDH-mutated cells show altered survival, motility, invasiveness and cell differentiation. In AML, IDH1 mutations might be present in 10-15% at diagnosis Ivosidenib (IVO) a first-in-class, oral, irreversible inhibitor of mutant IDH1 has shown clinical activity as a single agent in studies involving patients with IDH1 mutated relapsed or refractory (R/R) AML and in front line settings. In phase II clinical trials, IVO yielded 30-35% of complete response rates both in frontline and R/R settings, with long lasting responses. Based on these results, the FDA (Food and Drug Agency) gave its approval for newly-diagnosed AML IDH1mut patients who are ≥ 75 years old or who have comorbidities and in R/R. However, European Medicines Agency (EMA)'s did not approved IVO due to lack of evidences to support the application. Agios Netherlands B.V. (the company that previously own the drug before Servier Laboratories) withdrew its EMA application. Nevertheless, IVO has been available in France through a compassionate use program (CUP), since February 2020 for R/R patients and March 2022 for first line treatment. In this multicentric retrospective study, sponsor aim to evaluate the efficacy and safety of Ivo in two cohorts of IDH1mut AML patients treated within the CUP. The first cohort will concern patients treated in first line setting and the second cohort those treated in R/R disease. Results might provide new insights regarding IVO in real life settings and support signs of efficacy. This could provide new data for the haematologist community and for another appliance to grant EMA approval of IVO in the setting of R/R IDH1mut AML.
n/a
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT04623944 -
NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
|
Phase 1 | |
Not yet recruiting |
NCT06313437 -
Revumenib in Combination With 7+3 + Midostaurin in AML
|
Phase 1 | |
Terminated |
NCT04079738 -
Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib
|
Phase 1/Phase 2 | |
Recruiting |
NCT06052813 -
A Study of BN104 in the Treatment of Acute Leukemia
|
Phase 1/Phase 2 | |
Recruiting |
NCT06027853 -
Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia
|
Phase 1 | |
Completed |
NCT02986620 -
Italian Registry on the Prevalence of IDH1/IDH2 Mutations in Patients With Acute Myeloid Leukemia
|
||
Recruiting |
NCT05601466 -
Natural Killer(NK) Cell Therapy for Acute Myeloid Leukemia
|
Phase 1 | |
Recruiting |
NCT06066905 -
A Study of Chidamide With AZA in MRD Positive AML After Transplant
|
N/A | |
Recruiting |
NCT05909501 -
Assessment of Geriatric Evaluations Impact on New AML Guidance
|
||
Terminated |
NCT04614636 -
FT538 in Subjects With Advanced Hematologic Malignancies
|
Phase 1 | |
Not yet recruiting |
NCT06420063 -
Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML
|
Phase 1/Phase 2 | |
Withdrawn |
NCT04128020 -
Azacitidine Plus Nivolumab Following Reduced-intensity Allogeneic PBSC Transplantation for Patients With AML and High-risk Myelodysplasia
|
Phase 1 | |
Active, not recruiting |
NCT04749355 -
Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS
|
Phase 2 | |
Active, not recruiting |
NCT04755244 -
A Study of Evorpacept (ALX148) With Venetoclax and Azacitidine for Acute Myeloid Leukemia (ASPEN-05)
|
Phase 1/Phase 2 | |
Completed |
NCT03194685 -
Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
|
Phase 1/Phase 2 | |
Recruiting |
NCT03884829 -
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS
|
Phase 1 | |
Active, not recruiting |
NCT05177731 -
Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML
|
Phase 3 | |
Recruiting |
NCT05025098 -
Precision Therapy Versus Standard Therapy in AML and MDS in Elderly
|
Phase 2 | |
Not yet recruiting |
NCT06263387 -
Results From a French Temporary Utilization Authorization of First-line Acute Myeloid Leukemia (AML) Patients Ineligible for Intensive Chemotherapy (IC), Treated With Venetoclax Azacitidine
|
||
Not yet recruiting |
NCT06297772 -
Compare the Efficacy and Safety of Dec-FB4 and FB4 as Conditioning Regimen for AML-MR
|
Phase 3 |