Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Anemia

Anemia, Aplastic

Myeloproliferative Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Bone Marrow Failure Disorders

Pancytopenia

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Aplastic Anemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Wen-Chien Chou, MD, PhD

Chi-Yuan Yao, MD, MSc

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.

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.

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).

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

Data sharing and collaboration possibilities will be discussed upon request.

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.

National Taiwan University Hospital

Dermatologic Agents

All Drugs and Chemicals

Coal Tar

Participant's molecular profile shows that they have a gene mutation that may benefit from study drugs that are believed to target their gene mutation. Participant assigned to Arm A and will receive these targeted drugs.

Participant's molecular profile shows that they do not have a gene mutation. Participant assigned to Arm B in which doctor chooses a therapy based on other studies rather than gene mutation.

Treatment Based on Genetic Mutation

Treatment Based on No Genetic Mutation

Apostolia M. Tsimberidou, MD, PHD

The goal of this laboratory research study is to learn if using molecular information (matched therapy) or not using molecular information and having the study doctor choose the therapy based on your past experience are more effective ways to choose the best cancer treatment for you.

This is an investigational study.

Up to 200 participants will take part in this study. Up to 50 will be enrolled at MD Anderson.

If you agree to take part in this study, your tumor tissue and blood samples will be tested for molecular profiling. Molecular profiling is the classification of tissue based on the expression of certain genes within a tumor compared to normal tissue. This may be used to predict how the tumor responds to therapy. Your doctor may use the results of the molecular profiling to help decide which treatment might be the most beneficial for the disease.

Study Procedures:

Blood (about 2 teaspoons) will be drawn and you will have a tumor biopsy and a biopsy of normal tissue when you enroll in this study. Blood (about 2 teaspoons) will be drawn again about 2-3 weeks after you begin treatment. The type of biopsy you have will depend on the type of disease you have. The risks of this procedure will be discussed in more detail with you.

If there is not enough tissue with which the study doctor can perform the study tests (described below), you may need to have a second biopsy. The study staff will discuss this with you if it is needed.

Treatment Arms:

A series of tests to find which gene mutations you have, if any, will be performed. Depending on the results of your molecular testing, you may be enrolled on 1 of 2 arms.

If your molecular profile shows that you have a gene mutation that may benefit from study drugs that are believed to target your gene mutation, you will be enrolled in Arm A and will receive these targeted drugs.

If your molecular profile shows that you do not have a gene mutation, you will be enrolled in Arm B. In Arm B, the doctor will choose a therapy based on other studies rather than gene mutation.

Length of Study:

This study will last about 2 years. Your participation on this study will be complete after the last blood draw and tumor biopsy is collected.

Blood (about 2 teaspoons) drawn initially and again about 2-3 weeks after chosen treatment begins.

Rational Therapeutics Based on Matched Tumor and Normal Tissue

A Study to Select Rational Therapeutics Based on the Analysis of Matched Tumor and Normal Biopsies in Subjects With Advanced Malignancies

Progression-free survival (PFS) of the last therapeutic line (PFS1) before entering into study, with the PFS2 under study treatment. A clinical meaningful improvement is defined as demonstrating a PFS ratio (PFS2/PFS1) of being 1.5 or better.

European Commission

M.D. Anderson Cancer Center

Digestive System Diseases

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Neuroendocrine Tumors

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Adenoma

Adenoma, Islet Cell

Endocrine Gland Neoplasms

Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia Type 1

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Glandular and Epithelial

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Neoplasms, Multiple Primary

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Pancreatic Cancer

Hormones

Retrospective review of a prospectively maintained MEN1 database.

Participants sent an email questionnaire to complete regarding their pregnancy and hormone use history.

Database reviewed to obtain patient and disease characteristics, laboratory values, imaging results, hormone parameters (menopausal status, bioidentical hormone use, oral contraception use, gestational status and diagnosis of a prolactinoma) and vital status.

Chart Review

Participants sent an email questionnaire to complete regarding their pregnancy and hormone use history.

Questionnaire

Nancy D. Perrier, MD

OBJECTIVES:

The primary objective of this study is to evaluate the effect of estrogen on the development of the PNET in MEN1 patients.

The secondary objective is to evaluate the overall survival and disease specific survival in patients who have confirmed MEN1 with or without PNET and a pancreatic neuroendocrine tumor in relation to their hormone status. The secondary objective is to evaluate clinicopathologic features in relation to hormone status.

Retrospective review of a prospectively maintained MEN1 database. The patient cohort consists of all patients with confirmed MEN1 with or without PNET who are included in the database. The database will be reviewed to obtain patient and disease characteristics, laboratory values, imaging results, hormone parameters (menopausal status, bioidentical hormone use, oral contraception use, gestational status and diagnosis of a prolactinoma) and vital status.

For the prospective portion of this study, investigators want to see the impact of estrogen on the PNET forming and progression, and would like to use two equations to assess the estrogen exposure, so investigators should collect the information of menopause, menarche, breast feed, HRT, OCP use and pregnancy. To this end, investigators will contact female patients in the database who are still living, and obtain verbal informed consent to send an email questionnaire regarding their pregnancy and hormone use history.

Overall and Disease Specific Survival in Patients With Confirmed MEN1 With or Without PNET (Pancreatic Neuroendocrine Tumors)

Time to PNET calculated starting from the date of menarche time to the PNET diagnostic date or the menopause date (for the patients who get the menopause prior to the PNET diagnosis) or the last follow-up date.

Overall survival estimated and plotted using Kaplan-Meier method (Kaplan, 1958)(4).

Recurrence

determine the mutation profile of resected colorectal neoplasia

colonoscopy

Stepan Suchanek, assoc. prof.

Tomas Grega, MD, Ph.D.

Stepan Suchanek, MD., Ph.D.

Ondrej Ngo, Mgr.

Lucie Benesova, RNDr.

Ondrej Majek, RNDr.

Tereza Halkova, Mgr.

It is known that the development of colorectal adenoma is dependent on the appearance of somatic mutations in protooncogenes and tumor suppressor genes. Based on our previous mutation analyses of 120 patients with high-risk adenoma removed by enbloc resection with subsequent colonoscopy after 1 year, there is a correlation between mutation in exon 7 of the TP53 gene and risk of early metachronous lesions development. The results also indicate that mutation phenotype (mutation profile and burden) of all lesions detected on index colonoscopy can determine risk of metachronous lesions. As not all synchronous lesions were analyzed and the surveillance colonoscopy interval was less than 3 years, this assumption could not be confirmed. In this study it is planned to perform mutation analysis of all synchronous lesions in 200 patients and correlate the data with appearance of metachronous lesions after 1, 3 and 5 years. Moreover, the mutation profile of all metachronous lesions developed during the 5 years of surveillance will be determinated and compared with mutation profile of index lesions from the same localization to verify their common biological origin. This all could help personalize the surveillance program in terms of reduction of the burden on the patient and endoscopic workplaces and risk of developing colorectal cancer in a particular patient.

The aim of this prospective study is to identify patients with recurrent colorectal lesions risk and try to design an optimal intervals of surveillance colonoscopies, especially in the high-risk group of patients, using mutation and clinical-pathologic phenotype. The partial goals are: 1. Determination of the mutation profile and mutation burden in 200 patients based on examination of all their index and synchronous lesions found during index colonoscopy using an established PCR/DCE-based heteroduplex method. 2. Clinical and histopathological evaluation and mutational profiling of all metachronous lesions found during five-year surveillance period. 3. Correlation of clinical and histopathological parameters with mutational phenotype of patient. 4. Correlation of patient's mutational phenotype with an occurrence of metachronous lesion/s during surveillance period. 5. Comparison of the mutation profile of lesions from the index period withthe mutation profile of metachronous lesions. 6. Analysis of the similarity of the mutation profile of lesions found in the same / close areas of the colorectum.

Innovative Approach to Detect Recurrent Colorectal Lesions With Surveillance Via Mutation Analysis & Clinical Phenotype

Development and Clinical Utility of a New Method to Identify Patients With Risk of Recurrent Colorectal Lesions and Personalization of Their Surveillance Based on Mutation Burden and Clinical-pathological Phenotype

Correlation of clinical and histopathological parameters with mutational phenotype of patient.

Correlation of patient's mutational phenotype with an occurrence of metachronous lesion/s during surveillance period.

Analysis of the similarity of the mutation profile of lesions found in the same / close areas of the colorectum.

To identify patients with high risk of metachronous colorectal lesions and try to design and optimal intervals of surveillance colonoscopies, especially in the high-risk group of patients, using mutation and clinical-pathologic phenotype.

Determination of the mutation profile and mutation burden in 200 patients based on examination of all their index and synchronous lesions found during index colonoscopy using an established PCR/DCE-based heteroduplex method.

Clinical and histopathological evaluation and mutational profiling of all metachronous lesions found during five-year surveillance period.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Screening Gene Mutations in Myeloid Cancers by Next Generation Sequencing to Improve Treatment Results	NCT04060485	Acute Myeloid L... Myelodysplastic... Myeloproliferat... Aplastic Anemia		18 Years - 120 Years	National Taiwan University Hospital
Rational Therapeutics Based on Matched Tumor and Normal Tissue	NCT02272595	Advanced Cancer...	Treatment Based... Treatment Based...	18 Years -	M.D. Anderson Cancer Center
Overall and Disease Specific Survival in Patients With Confirmed MEN1 With or Without PNET (Pancreatic Neuroendocrine Tumors)	NCT03043508	Genetic Mutatio... MEN1	Chart Review Questionnaire	18 Years -	M.D. Anderson Cancer Center
Innovative Approach to Detect Recurrent Colorectal Lesions With Surveillance Via Mutation Analysis & Clinical Phenotype	NCT05929365	Predictive Canc...	colonoscopy	18 Years - 75 Years	Military University Hospital, Prague
Rational Therapeutics Based on Matched Tumor and Normal Tissue	NCT02272595	Advanced Cancer...	Treatment Based... Treatment Based...	18 Years -	M.D. Anderson Cancer Center
Overall and Disease Specific Survival in Patients With Confirmed MEN1 With or Without PNET (Pancreatic Neuroendocrine Tumors)	NCT03043508	Genetic Mutatio... MEN1	Chart Review Questionnaire	18 Years -	M.D. Anderson Cancer Center

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