Screening Gene Mutations in Myeloid Cancers by Next Generation Sequencing to Improve Treatment Results

Genetic mutations have closely linked to the pathogenesis and prognostication of myeloid cancers. In addition, a number of molecularly targeted agents have been developed in recent years. With the advent of next generation sequencing (NGS), we now are able to detect a wide range of mutations more rapidly, accurately, and economically. In this study, the investigators will use NGS to screen and analyze myeloid-associated gene mutations in the participants, and aim to build up the mutational landscapes of the various myeloid cancers, and investigate how these mutations are linked to clinical outcome.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Aplastic Anemia; Myeloproliferative Neoplasm

Detailed Description

Genetic mutations have closely linked to the pathogenesis and prognostication of myeloid cancers (including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms). In recent years, a number of novel therapeutic agents targeting various genetic mutations have been developed. For instance, patients with FLT3-ITD and IDH2 mutations have been shown to derive benefits from midostaurin and enasidenib, respectively. Furthermore, the TP53-mutated patients once categorized in the very high risk group, have been found to respond favorably to the hypomethylating agent, decitabine. Detecting a wide array of cancer mutations nowadays by the traditional Sanger method has become not only time-consuming but also not as cost-effective. With the advent of next generation sequencing (NGS), we now are able to detect a panel gene mutations more rapidly, accurately, and economically.

In this study, the investigators will screen and analyze myeloid-associated gene mutations in participants with myeloid cancers, with an in-house designed targeted NGS panel. The total nucleic acid from patients' blood or bone marrow specimens will be extracted, and then subjected to the library preparation procedure based on multiplex PCR amplification. Sequencing will be performed on Illumina MiSeq sequencer, and the results will be analyzed using our in-house developed bioinformatic workflow. Briefly, the sequenced reads will be aligned to human reference genome hg19 with BWA-mem, and somatic mutations called with Mutect2. The variants will be annotated via SnpEff with RefSeq, dbSNP, 1000 Genome Project, COSMIC and ClinVar databases. The investigators aim to build up the mutational landscapes of the above mentioned myeloid cancers, and investigate how these mutations are linked to clinical outcome.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Wen-Chien Chou, MD, PhD; Phone Number: +886-972651701; Email: wchou@ntu.edu.tw
• Study Contact Backup: Name: Chi-Yuan Yao, MD, MSc; Phone Number: +886-972655691; Email: Y06960@ms1.ylh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Wen-Chien Chou, MD, PhD; Phone Number: +886-972651701; Email: wchou@ntu.edu.tw
    • Contact: Chi-Yuan Yao, MD, MSc; Phone Number: +886-972655691; Email: Y06960@ms1.ylh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult myeloid cancer (including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms) patients (newly diagnosed or relapsed) diagnosed at the National Taiwan University Hospital (NTUH) according to the updated 2016 WHO myeloid disease classification.

Description

Inclusion criteria:

1. Patients ≥ 18 years of age diagnosed with myeloid cancers (including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms).
2. Healthy Volunteers ≥ 18 years of age.
3. Participants must be willing to provide voluntary written informed consent before study related procedures.

Exclusion criteria:

1. Patients ≥ 18 years of age diagnosed with non-myeloid cancers.
2. Patients <18 years of age diagnosed with myeloid cancers (including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of various genetic mutations in myeloid cancers	Peripheral blood or marrow blood will be obtained from routine practice blood/marrow sampling specimens (no extra venipuncture or bone marrow aspiration would be required) and sent for NGS analyses.	5 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Wen-Chien Chou, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 19, 2019
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Prognosis; Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Neoplasm; Genetic mutation; Next generation sequencing; Aplastic Anemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Anemia; Precancerous Conditions; Leukemia; Bone Marrow Failure Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myeloproliferative Disorders; Anemia, Aplastic
• Other Study ID Numbers: 201803002RIPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing and collaboration possibilities will be discussed upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No