NCT04369287: Euro_IDH_AML

Prevalence and Clinical Effect of IDH1/2 Mutations in Patients With Acute Myeloid Leukemia

Status unknown Last updated 13 May 2020

What this trial tests

trial in Acute Myeloid Leukemia in 654 participants. Status unknown.

Timeline

1 January 2016

Primary endpoint
15 October 2020

15 December 2020

Quick facts

Lead sponsor	Istituto Clinico Humanitas
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	654
Start date	1 January 2016
Primary completion	15 October 2020
Estimated completion	15 December 2020
Sites	1 location across Italy

Conditions studied

• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →
• IDH1 Gene Mutation — all drugs for IDH1 Gene Mutation →
• IDH2 Gene Mutation — all drugs for IDH2 Gene Mutation →

Sponsor

Istituto Clinico Humanitas

Who can join

Adults 18 to 90, any sex, with Acute Myeloid Leukemia or IDH1 Gene Mutation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Among the most notable cancer genome-wide sequencing discoveries in recent years was the finding of mutation hot-spots in the isocitrate dehydrogenase (IDH) genes in grade II/III astrocytomas and oligodendrogliomas and in secondary glioblastomas. This was rapidly followed by identification of recurrent IDH1/2 mutations in myeloid neoplasms (MN), including acute myeloid leukemia (AML). Mutant IDH is now a therapeutic target of great interest in cancer research, especially in AML, given the limitations of current approved therapies and the encouraging early clinical data demonstrating proof of concept for investigational mutant IDH1/2 inhibitors.

The origin of mutations in AML was explored by investigating the clonal evolution of genomes sequenced from patients with M1- or M3-AML and comparing them with hematopoietic stem/progenitor cells (HSPCs) from healthy volunteers. Six genes were found to have statistically higher mutation frequencies in M1 versus M3 genomes (NPM1, DNMT3A, IDH1, IDH2, TET2 and ASXL1), suggesting they are initiating rather than cooperating events. Prospective evaluation of serial 2- HG levels during treatment of newly diagnosed AML treated with standard chemotherapy revealed that both 2-HG level and mutated IDH allele burden decreased with response to treatment but began to rise again as therapy failed.

The prognostic impact of IDH mutations in AML is under continued investigation and varies across studies. In this research project authors aim a) to define the prevalence and type of IDH1/2 mutations in AML patients; b) to define relationships between IDH1/2 mutations and other oncogenic mutations in AML, as well as to describe clonal evolution of the disease and c) to describe the clinical outcome of IDH1/2 mutated patients with AML treated with currently available treatments.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.