Acute Myeloid LeukemiaEuro_IDH_AMLNCT04369287
Prevalence and Clinical Effect of IDH1/2 Mutations in Patients With Acute Myeloid Leukemia
An observational study of Acute Myeloid Leukemia and IDH1 Gene Mutation, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Myeloid Leukemia, IDH1 Gene Mutation, IDH2 Gene Mutation
- How many people
- 654 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2016to 15 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: IDH 1/2 mutated patients, IDH not mutaded patients
Who may be able to join
- Age ≥ 18 years
- Diagnosis of AML According to 2016 WHO classification criteria
- Ability to give informed consent according to ICH/EU GCP, and national/local regulations.
Who cannot join
- Lack of written informed consent
- Lack of biological samples (blood, bone marrow aspirate)
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Milan
Marilena Bicchieri, PhD, +390282247668 ext. +39, marilena.bichieri@cancercenter.humanitas.it
About this study
Official title: Prevalence, Correlation With Other Mutant Genes and Clinical Effect of IDH1/2 Mutations in Patients With Acute Myeloid Leukemia. The European IDH Research Alliance
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.
Read the detailed 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), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
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.
There is evidence to suggest that IDH mutations may cooperate with other mutations to initiate and drive oncogenesis in myeloid malignancies. High levels of 2-hydroxyglutarate (2-HG, as a result of gene mutation) have been shown to inhibit αKG-dependent dioxygenases including histone and DNA demethylases, proteins that regulate cellular epigenetic status. Consistent with 2-HG promoting cancer via an effect on chromatin structure, tumors harboring IDH mutations display a CpG island methylator phenotype. More recent studies have shown that overexpression of mutant IDH enzymes can induce histone and DNA hypermethylation, as well as block cellular differentiation. Together, these data suggest that cancer-associated IDH mutations can induce a block in cellular differentiation through epigenetic modifications, which contributes to tumor initiation and progression, and thus support the clinical evaluation of agents targeted to mutant IDH
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. Furthermore, all of these genes have been shown to play a role in chromatin modification, suggesting that epigenetic alterations may function to initiate tumorigenesis.
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, the authors aim:
- To define the prevalence and type of IDH1/2 mutations in acute myeloid leukemias.
- To define genotype-phenotype relationship in IDH1/2 mutated patients.
- To define relationships between IDH1/2 mutations and other oncogenic mutations in AML, as well as to describe clonal evolution of the disease (including the evaluation of genotype at disease relapse).
- To describe the clinical outcome of IDH1/2 mutated patients with AML treated with currently available treatments.
- Keywords
- AML, IDH1 gene, IDH2 gene, gene mutation
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| IDH1-mutated AML | Patients affected with AML and carryng IDH1 mutations | |
| IDH2-mutated AML | Patients affected with AML and carryng IDH2 mutations | |
| IDH1/2 unmutated AML | Patients affected with AML without IDH1/2 mutations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of IDH1/2 mutations in patients with AML
IDH1/2 mutational status will be analyzed in all centers by NGS or sanger sequencing on samples obtained from patients affected with AML enrolled in the study with the aim to provide information on the prevalence and type of IDH1/2 mutations
Measured: 2016-2020
genotype-phenotype correlations in AML patients carryng IDH1/2 mutations
Data obtained from targeted gene sequencing will be correlated with clinical and hematological variables of interest (i.e., demographic factors, WHO 2016 category, cytogenetics, presence of recurrent molecular abnormalities, response to treatment, overall survival, disease-free survival) to identify specific associations between genotype and disease phenotype)
Measured: 2016-2020
Overall survival in patients with AML carryng IDH1/2 mutations
Specific analyses will be carried out to describe overall survival of AML with IDH1/2 mutations with currently available treatments. Moreover, A comparison between survival of IDH-mutated vs. IDH-unmutated patients will be performed
Measured: 2016-2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start1 Jan 2016
- Primary completion15 Oct 2020 (estimated)
- Study completion15 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 654 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Sponsor
- Investigators
- Francesc Sole, MD, Principal investigator, Josep Carreras Leukaemia Research InstituteJoana Desterro, Principal investigator, Instituto Português de Oncologia de LisboaKlaus Metzeler, Principal investigator, Laboratory for Leukemia Diagnostics. University of MunichPau Montesinos, Principal investigator, Hematology Department. Hospital Universitari i Politècnic La FeJorge Sierra, Principal investigator, Hospital de la Santa Creu i Sant Pau Autonomous University of Barcelona, SpainMatteo Della Porta, MD, Study chair, Humanitas Research Hospital IRCCS, Rozzano-MilanMaria Teresa Voso, Principal investigator, Fondazione GIMEMAChristoph Roellig, Principal investigator, Technische Universität Dresden | TUD · Medical Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369287
- Sponsor's protocol ID
- ONC/OSS-04/2016
- Acronym
- Euro_IDH_AML
- Status last verified
- May 2020
- First submitted
- 27 Apr 2020
- Last updated
- 13 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Larsson CA, Cote G, Quintas-Cardama A. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res. 2013 Aug;11(8):815-27. doi: 10.1158/1541-7786.MCR-12-0695. Epub 2013 May 3.
PubMed 23645565Chou WC, Lei WC, Ko BS, Hou HA, Chen CY, Tang JL, Yao M, Tsay W, Wu SJ, Huang SY, Hsu SC, Chen YC, Chang YC, Kuo KT, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF. The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia. Leukemia. 2011 Feb;25(2):246-53. doi: 10.1038/leu.2010.267. Epub 2010 Nov 16.
PubMed 21079611DiNardo CD, Ravandi F, Agresta S, Konopleva M, Takahashi K, Kadia T, Routbort M, Patel KP, Mark Brandt, Pierce S, Garcia-Manero G, Cortes J, Kantarjian H. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol. 2015 Aug;90(8):732-6. doi: 10.1002/ajh.24072.
PubMed 26016821Thol F, Damm F, Wagner K, Gohring G, Schlegelberger B, Hoelzer D, Lubbert M, Heit W, Kanz L, Schlimok G, Raghavachar A, Fiedler W, Kirchner H, Heil G, Heuser M, Krauter J, Ganser A. Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood. 2010 Jul 29;116(4):614-6. doi: 10.1182/blood-2010-03-272146. Epub 2010 Apr 26.
PubMed 20421455Cancer Genome Atlas Research Network; Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, Hoadley K, Triche TJ Jr, Laird PW, Baty JD, Fulton LL, Fulton R, Heath SE, Kalicki-Veizer J, Kandoth C, Klco JM, Koboldt DC, Kanchi KL, Kulkarni S, Lamprecht TL, Larson DE, Lin L, Lu C, McLellan MD, McMichael JF, Payton J, Schmidt H, Spencer DH, Tomasson MH, Wallis JW, Wartman LD, Watson MA, Welch J, Wendl MC, Ally A, Balasundaram M, Birol I, Butterfield Y, Chiu R, Chu A, Chuah E, Chun HJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Jones S, Karsan A, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall K, Parker J, Pleasance E, Plettner P, Schein J, Stoll D, Swanson L, Tam A, Thiessen N, Varhol R, Wye N, Zhao Y, Gabriel S, Getz G, Sougnez C, Zou L, Leiserson MD, Vandin F, Wu HT, Applebaum F, Baylin SB, Akbani R, Broom BM, Chen K, Motter TC, Nguyen K, Weinstein JN, Zhang N, Ferguson ML, Adams C, Black A, Bowen J, Gastier-Foster J, Grossman T, Lichtenberg T, Wise L, Davidsen T, Demchok JA, Shaw KR, Sheth M, Sofia HJ, Yang L, Downing JR, Eley G. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013 May 30;368(22):2059-74. doi: 10.1056/NEJMoa1301689. Epub 2013 May 1.
PubMed 23634996Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12.
PubMed 24030381Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010 Mar 16;17(3):225-34. doi: 10.1016/j.ccr.2010.01.020. Epub 2010 Feb 18.
PubMed 20171147Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, Sasaki M, Jin S, Schenkein DP, Su SM, Dang L, Fantin VR, Mak TW. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010 Feb 15;207(2):339-44. doi: 10.1084/jem.20092506. Epub 2010 Feb 8.
PubMed 20142433DiNardo CD, Propert KJ, Loren AW, Paietta E, Sun Z, Levine RL, Straley KS, Yen K, Patel JP, Agresta S, Abdel-Wahab O, Perl AE, Litzow MR, Rowe JM, Lazarus HM, Fernandez HF, Margolis DJ, Tallman MS, Luger SM, Carroll M. Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4917-24. doi: 10.1182/blood-2013-03-493197. Epub 2013 May 2.
PubMed 23641016Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJ, Thompson CB, Levine RL, Melnick A. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010 Dec 14;18(6):553-67. doi: 10.1016/j.ccr.2010.11.015. Epub 2010 Dec 9.
PubMed 21130701Ye D, Xiong Y, Guan KL. The mechanisms of IDH mutations in tumorigenesis. Cell Res. 2012 Jul;22(7):1102-4. doi: 10.1038/cr.2012.51. Epub 2012 Mar 27.
PubMed 22453240Wang F, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, Yang H, Gross S, Artin E, Saada V, Mylonas E, Quivoron C, Popovici-Muller J, Saunders JO, Salituro FG, Yan S, Murray S, Wei W, Gao Y, Dang L, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, de Botton S, Yen KE. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6. doi: 10.1126/science.1234769. Epub 2013 Apr 4.
PubMed 23558173Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG Jr. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013 Mar 29;339(6127):1621-5. doi: 10.1126/science.1231677. Epub 2013 Feb 7.
PubMed 23393090Della Porta MG, Travaglino E, Boveri E, Ponzoni M, Malcovati L, Papaemmanuil E, Rigolin GM, Pascutto C, Croci G, Gianelli U, Milani R, Ambaglio I, Elena C, Ubezio M, Da Via' MC, Bono E, Pietra D, Quaglia F, Bastia R, Ferretti V, Cuneo A, Morra E, Campbell PJ, Orazi A, Invernizzi R, Cazzola M; Rete Ematologica Lombarda (REL) Clinical Network. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia. 2015 Jan;29(1):66-75. doi: 10.1038/leu.2014.161. Epub 2014 May 20.
PubMed 24935723
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence, Correlation With Other Mutant Genes and Clinical Effect of IDH1/2 Mutations in Patients With Acute Myeloid Leukemia. The European IDH Research Alliance
- ClinicalTrials.gov ID
- NCT04369287
- Acronym / sponsor ID
- Euro_IDH_AML / ONC/OSS-04/2016
- Keywords
- AML, IDH1 gene, IDH2 gene, gene mutation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 654 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- Celgene
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 15 Oct 2020 (estimated)
- Study completion
- 15 Dec 2020 (estimated)
- First posted
- 30 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
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.
There is evidence to suggest that IDH mutations may cooperate with other mutations to initiate and drive oncogenesis in myeloid malignancies. High levels of 2-hydroxyglutarate (2-HG, as a result of gene mutation) have been shown to inhibit αKG-dependent dioxygenases including histone and DNA demethylases, proteins that regulate cellular epigenetic status. Consistent with 2-HG promoting cancer via an effect on chromatin structure, tumors harboring IDH mutations display a CpG island methylator phenotype. More recent studies have shown that overexpression of mutant IDH enzymes can induce histone and DNA hypermethylation, as well as block cellular differentiation. Together, these data suggest that cancer-associated IDH mutations can induce a block in cellular differentiation through epigenetic modifications, which contributes to tumor initiation and progression, and thus support the clinical evaluation of agents targeted to mutant IDH
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. Furthermore, all of these genes have been shown to play a role in chromatin modification, suggesting that epigenetic alterations may function to initiate tumorigenesis.
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, the authors aim:
- To define the prevalence and type of IDH1/2 mutations in acute myeloid leukemias.
- To define genotype-phenotype relationship in IDH1/2 mutated patients.
- To define relationships between IDH1/2 mutations and other oncogenic mutations in AML, as well as to describe clonal evolution of the disease (including the evaluation of genotype at disease relapse).
- To describe the clinical outcome of IDH1/2 mutated patients with AML treated with currently available treatments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IDH1-mutated AML | – | –Patients affected with AML and carryng IDH1 mutations |
| IDH2-mutated AML | – | –Patients affected with AML and carryng IDH2 mutations |
| IDH1/2 unmutated AML | – | –Patients affected with AML without IDH1/2 mutations |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- IDH 1/2 mutated patients, IDH not mutaded patients
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- Diagnosis of AML According to 2016 WHO classification criteria
- Ability to give informed consent according to ICH/EU GCP, and national/local regulations.
Key exclusion criteria (2 listed)
- Lack of written informed consent
- Lack of biological samples (blood, bone marrow aspirate)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of IDH1/2 mutations in patients with AML
Time frame: 2016-2020
IDH1/2 mutational status will be analyzed in all centers by NGS or sanger sequencing on samples obtained from patients affected with AML enrolled in the study with the aim to provide information on the prevalence and type of IDH1/2 mutations
genotype-phenotype correlations in AML patients carryng IDH1/2 mutations
Time frame: 2016-2020
Data obtained from targeted gene sequencing will be correlated with clinical and hematological variables of interest (i.e., demographic factors, WHO 2016 category, cytogenetics, presence of recurrent molecular abnormalities, response to treatment, overall survival, disease-free survival) to identify specific associations between genotype and disease phenotype)
Overall survival in patients with AML carryng IDH1/2 mutations
Time frame: 2016-2020
Specific analyses will be carried out to describe overall survival of AML with IDH1/2 mutations with currently available treatments. Moreover, A comparison between survival of IDH-mutated vs. IDH-unmutated patients will be performed
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
- Results publication: PubMed 23645565Larsson CA, Cote G, Quintas-Cardama A. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res. 2013 Aug;11(8):815-27. doi: 10.1158/1541-7786.MCR-12-0695. Epub 2013 May 3.
- Results publication: PubMed 21079611Chou WC, Lei WC, Ko BS, Hou HA, Chen CY, Tang JL, Yao M, Tsay W, Wu SJ, Huang SY, Hsu SC, Chen YC, Chang YC, Kuo KT, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF. The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia. Leukemia. 2011 Feb;25(2):246-53. doi: 10.1038/leu.2010.267. Epub 2010 Nov 16.
- Results publication: PubMed 26016821DiNardo CD, Ravandi F, Agresta S, Konopleva M, Takahashi K, Kadia T, Routbort M, Patel KP, Mark Brandt, Pierce S, Garcia-Manero G, Cortes J, Kantarjian H. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol. 2015 Aug;90(8):732-6. doi: 10.1002/ajh.24072.
- Results publication: PubMed 20421455Thol F, Damm F, Wagner K, Gohring G, Schlegelberger B, Hoelzer D, Lubbert M, Heit W, Kanz L, Schlimok G, Raghavachar A, Fiedler W, Kirchner H, Heil G, Heuser M, Krauter J, Ganser A. Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood. 2010 Jul 29;116(4):614-6. doi: 10.1182/blood-2010-03-272146. Epub 2010 Apr 26.
- Results publication: PubMed 23634996Cancer Genome Atlas Research Network; Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, Hoadley K, Triche TJ Jr, Laird PW, Baty JD, Fulton LL, Fulton R, Heath SE, Kalicki-Veizer J, Kandoth C, Klco JM, Koboldt DC, Kanchi KL, Kulkarni S, Lamprecht TL, Larson DE, Lin L, Lu C, McLellan MD, McMichael JF, Payton J, Schmidt H, Spencer DH, Tomasson MH, Wallis JW, Wartman LD, Watson MA, Welch J, Wendl MC, Ally A, Balasundaram M, Birol I, Butterfield Y, Chiu R, Chu A, Chuah E, Chun HJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Jones S, Karsan A, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall K, Parker J, Pleasance E, Plettner P, Schein J, Stoll D, Swanson L, Tam A, Thiessen N, Varhol R, Wye N, Zhao Y, Gabriel S, Getz G, Sougnez C, Zou L, Leiserson MD, Vandin F, Wu HT, Applebaum F, Baylin SB, Akbani R, Broom BM, Chen K, Motter TC, Nguyen K, Weinstein JN, Zhang N, Ferguson ML, Adams C, Black A, Bowen J, Gastier-Foster J, Grossman T, Lichtenberg T, Wise L, Davidsen T, Demchok JA, Shaw KR, Sheth M, Sofia HJ, Yang L, Downing JR, Eley G. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013 May 30;368(22):2059-74. doi: 10.1056/NEJMoa1301689. Epub 2013 May 1.
- Results publication: PubMed 24030381Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesc Sole, MD principal investigator
Josep Carreras Leukaemia Research Institute
Joana Desterro principal investigator
Instituto Português de Oncologia de Lisboa
Klaus Metzeler principal investigator
Laboratory for Leukemia Diagnostics. University of Munich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Myeloid Leukemia and IDH1 Gene Mutation, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matteo Della Porta, MD (+390282247668 ext. +39, matteo.della_porta@hunimed.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of IDH1/2 mutations in patients with AML (time frame: 2016-2020). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04369287, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2020.