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

NCT04369287 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 654

Last updated 2020-05-13

No results posted yet for this study

Summary

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.

Conditions

Sponsors & Collaborators

  • Celgene

    collaborator INDUSTRY

  • Istituto Clinico Humanitas

    lead OTHER

Principal Investigators

  • Francesc Sole, MD · Josep Carreras Leukaemia Research Institute

  • Joana Desterro · Instituto Português de Oncologia de Lisboa

  • Klaus Metzeler · Laboratory for Leukemia Diagnostics. University of Munich

  • Pau Montesinos · Hematology Department. Hospital Universitari i Politècnic La Fe

  • Jorge Sierra · Hospital de la Santa Creu i Sant Pau Autonomous University of Barcelona, Spain

  • Matteo Della Porta, MD · Humanitas Research Hospital IRCCS, Rozzano-Milan

  • Maria Teresa Voso · Fondazione GIMEMA

  • Christoph Roellig · Technische Universität Dresden | TUD · Medical Clinic

  • Lisa Pleyer · Salzburg Cancer Reasearch Institute (SCRI), Cancer Cluster Salzburg (CCS)

  • Moritz Middeke · Technische Universität Dresden | TUD · Medical Clinic

Eligibility

Min Age
18 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-01-01
Primary Completion
2020-10-15
Completion
2020-12-15

Countries

  • Italy

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04369287 on ClinicalTrials.gov