Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions following standard international guidelines.

Tumor tissue processing and all NGS genotyping were performed at the Laboratory of Molecular Oncology (Hellenic Foundation for Cancer Research / AUTH). Paraffin H\&E sections from the retrieved tissue blocks were centrally reviewed for tumor histology and tissue adequacy for DNA extraction and were marked for macrodissection along with tumor DNA content \[(former tumor cell content (TCC%)\] assessment. DNA was extracted from macrodissected tissue fragments with the QIAamp® DNA mini kit (Qiagen, Hilden, Germany), measured in a Qubit fluorometer (Thermo Fisher Scientific, Paisley, UK), and genotyped with NGS in an Ion Torrent Proton sequencer (Thermo Fisher Scientific) by using a previously published custom panel (Kotoula, Lakis et al. 2019). Following stringent variant quality filtering (Kotoula, Chatzopoulos et al. 2021), 500 tumors

Tumor molecular profiling

ELENA FOUNTZILAS, MD

Molecular alterations in Homologous Recombination Repair (HRR) genes have been associated with clinical benefit from chemotherapy and/or Poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer. Therefore, the performance of tumor molecular profiling is currently recommended by international guidelines at initial diagnosis, among other reasons, for the modification of the treatment plan. The investigators' hypothesis was that tumor molecular profiling reveals additional parameters that can improve the predictive and prognostic role of the mere presence of HRR gene mutations. The study aimed to investigate the prognostic and predictive role of clonality of pathogenic variants in HRR genes and/or concurrent pathogenic variants in other clinically relevant genes.

Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

Clonality of Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

The time from ovarian cancer diagnosis to the date of death from any cause

The time from initiation of first-line chemotherapy to the first documented progression, death from any cause or last contact, whichever occurred first

Hellenic Cooperative Oncology Group

Heart and Blood Diseases

Blood and Lymph Conditions

Thrombosis

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

The cohort will be composed of PV and ET patients, some with a history of thrombosis and some without any history of thrombosis. A comparison will also be performed between patients with different MPN (PV or ET) and the type of thrombosis (venous, arterial, splanchnic)

A specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice

Blood sampling

Olivier MANSIER

François BOYER

Jean-Baptiste ROBIN

Pierre DUFFAU

Etienne GABRIEL

Eric LIPPERT

Clémentine SALVADO

Diane LARA

Samia MADENE

Chloé JAMES

Clémence MEDIAVILLA

Jean-François VIALLARD

Myeloproliferative Neoplasms (MPN) are associated with an increased risk of thrombosis. Platelets, red blood cells (RBC), leukocytes and endothelial cells are involved in these complications. An association with the JAK2V617F allele burden assessed in leukocytes has also been suggested. In some patients the allele burden measured in platelets and red blood cells is higher than the one determined in leukocytes. Our project aims at associating the risk of thrombosis with the allele burden determined in the cell populations (platelets, red blood cells, granulocytes and endothelial cells) and identifying high-risk clonality profiles.

Myeloproliferative Neoplasms (MPN) are hematological malignancies associated with an increased risk of thrombosis. Although different cell types have been involved in these complications (platelets, red blood cells, leucocytes and endothelial cells), there do not exist any reliable biomarker to predict the thrombotic risk in MPN patients. While some studies suggested that the JAK2V617F allele burden measured in leukocytes was associated with the risk of thrombosis, other studies did not confirm these results. Besides, a recent work demonstrated that in some patients, the JAK2V617F allele burden measured in platelets and red blood cells was higher than the one determined in leukocytes. Moreover, some patients present JAK2V617F mutated endothelial cells, known as pro-thrombotic in in vitro and animal models. The CLOJAK project will search for an association between the thrombotic risk in MPN and the proportion of cells carrying the JAK2V617F mutation in erythroid cells and platelets or its presence in endothelial cells. The objective is to determine a clonality profile (i.e. the profile of repartition of the JAK2V617F allele burden in the different hematopoietic and endothelial lineages) associated with the occurrence of thrombosis in MPN patients.

One hundred and twenty PV and ET patients will be studied at diagnosis. Their platelets, red blood cells, granulocytes and endothelial cells will be isolated. The JAK2V617F allele burden will be measured in these cells thanks to a digital PCR technic. An association between the clonality profile and the existence of a thrombosis at diagnosis, the MPN phenotype (PV or ET), the IPSET-thrombosis score and the type of thrombosis (venous, arterial, splanchnic) will be searched.

Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)

History of thrombosis at MPN diagnosis defined as the occurrence of a venous (deep vein thrombosis, pulmonary embolism) or arterial thrombosis (ischemic stroke or myocardial infarction) or a thrombosis in the splanchnic area

The clonality profile defined based on the association of cell lineages in which a JAK2V617F allele burden over 25% is measured together with the detection (or not) of the JAK2V617F mutation in endothelial cells

University Hospital, Bordeaux

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Hypertension

Neoplasm Metastasis

Congenital Abnormalities

Pulmonary Arterial Hypertension

Hypertension, Pulmonary

Primary Myelofibrosis

Familial Primary Pulmonary Hypertension

Vascular Diseases

Neoplastic Processes

Lung Diseases

Respiratory Tract Diseases

Antihypertensive Agents

Platelet Aggregation Inhibitors

All Drugs and Chemicals

Vasodilator Agents

Epoprostenol

Tezosentan

Subjects diagnosed with primary pulmonary hypertension (PPH)

Subjects diagnosed with Primary or Secondary Myelofibrosis

Josef T Prchal, MD

To determine the prevalence of myelofibrosis in patients with primary pulmonary hypertension, and to discover if the fibrosis in these patients is primary (AMM) or secondary.

Pulmonary arterial hypertension: Pulmonary arterial hypertension (PAH) is a disease primarily affecting the small precapillary pulmonary vessels. It is characterized by sustained elevation of the pulmonary vascular resistance (PVR). Without therapy, right heart failure and death eventually occur. PAH occurs in an idiopathic form, primary pulmonary hypertension (PPH), and in association with other disorders such as connective tissue diseases or congenital heart disease (CHD). PAH remains a disease of unknown etiology. Until recently, prognosis for PAH was poor, with a median survival of less than 3 years.

Prostacyclin (PGI2) is the main product of arachidonic acid in all vascular endothelium. It is a potent vasodilator in all vascular beds. In addition, it is a potent endogenous inhibitor of platelet aggregation and smooth muscle growth. The prostacyclin receptor (IP) is located on a variety of cell types, enabling prostacyclin to exert a range of biologic actions by means of raising intracellular levels of cAMP through activation of adenylate cyclase. The stable, freeze-dried salt preparation of prostacyclin is known as epoprostenol and is available for IV administration under the brand name Flolan (Glaxo Wellcome, Research Triangle Park, N.C.). The first randomized clinical trial in PPH showed that epoprostenol improved quality of life, hemodynamics, exercise tolerance, and survival over a 12-week period. Epoprostenol has become the standard of care for patients with advanced PPH. Recently, chronic intravenous epoprostenol has been shown to be an effective therapy to improve long-term quality of life and survival in patients with PPH. Epoprostenol also improves hemodynamics, exercise capacity, and quality of life (but not survival) in PAH associated with CHD and connective tissue disease.

Side effects of epoprostenol infusion include rash, headache, jaw pain, leg pain, diarrhea, nausea, catheter infections, chest pain, anxiety dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, tachycardia, flu-like symptoms, and anxiety/nervousness. Thrombocytopenia is commonly seen in patients with PPH treated with PG12. Occasionally, a decrease in other blood cell lines occurs leading to anemia or pancytopenia. Splenomegaly and hypersplenism are observed at times. While thrombocytopenia has been attributed to the antiplatelet effects of prostacyclin, the pathophysiology of pancytopenia is poorly understood. There are no studies that address thrombocytopenia and other hemopoietic abnormalities in people with pulmonary hypertension receiving epoprostenol. The possibility of myelofibrosis causing these hematologic abnormalities has not been investigated.

Primary myelofibrosis is a myeloproliferative disorder, characterized typically by pancytopenia, splenomegaly, a leukoerythroblastic blood smear, fibrosis on the bone marrow examination, and myeloid metaplasia. Like all myeloproliferative disorders, it is due to somatic mutation and clonal proliferation of hematopoietic progenitors. Fibrosis occurs secondary to cytokines secreted by malignant cells. These patients are symptomatic because of cytopenias. Bone marrow failure and transformation to acute myeloid leukemia is the major reason for mortality in these patients. Elevated blood levels of hematopoietic progenitors (identified by positivity for the CD34 antigen) are well documented and correlates with prognosis. Therefore two major identifying features of primary myelofibrosis as opposed to secondary fibrosis of the marrow are: 1) clonal hematopoiesis and 2) high CD 34 positive hematopoietic precursors.

We therefore hypothesize these two will be normal in patients with secondary myelofibrosis and help us distinguish the two entities.

Clonality Studies: Clonality is based on the principal of X-chromosome inactivation and thus, for clonality studies only females can be used as subjects. It is based on the principal that while female cells have two X-chromosomes, one is randomly inactivated during early embryonic development and thus female tissue is a mixture of cells expressing either paternal or maternal inherited x-chromosome genes. In the first step, DNA analysis will study 5 exonic polymorphisms for the X-chromosome genes which have previously been shown to be useful for these purposes. If any of the five loci is heterozygous then the subject is said to be informative for clonality. Studies which will proceed as follows: The fresh blood platelets and granulocytes will be isolated and the RNA isolated and used later for reverse transcription to cDNA which will then be analyzed for X-chromosome allelic usage ratio by single-stranded conformational polymorphisms (SSCP). If only one allele is expressed in platelets or granulocytes the patient is said to be clonal and favors a diagnosis of myeloproliferative disorder (such as AMM), while polyclonal blood (both X-chromosome alleles expressed in platelets and granulocytes) is compatible with secondary myelofibrosis.

A three-color direct immunofluorescent staining method will be used in the evaluation of CD34+ cells. In our preliminary experience we observed four Flolan treated patients with PPH who had splenomegaly, anemia and/or thrombocytopenia. All of these patients had severe marrow fibrosis. The purpose of this study is to determine whether the incidence of the bone marrow fibrosis in this patient population is primary or secondary, and whether a secondary effect is a fibrosis that would be expected to be transient and resolve after discontinuation of Flolan.

Participating subjects will Patients will undergo the following studies:

1. History and Physical examination
2. Peripheral blood smear
3. Bone marrow examination to determine the presence and severity of fibrosis. The bone marrow specimen taken for diagnostic purposes will be examined by three independent hematologists/hematopathologists in a masked fashion for the presence of fibrosis using routine methods.
4. Blood: 30 cc of blood will be collected for

   1. Clonality studies (female subjects only),
   2. CD34 quantitation.
   3. Further studies will be done to monitor the aberrant trafficking of hemopoietic stem cells, the adhesion molecules, and any disease related genes, such as JAK2V617F and cMPL, if indicated.
   4. The above studies will be repeated in patients undergoing lung transplants at 3 months, 6 months and 1 year after transplantation.

Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder

National Cancer Institute (NCI)

University of Utah

Chromosome Aberrations

Chromosome Disorders

Genetic Diseases, Inborn

The referring haematologist will suggest that the patient participate in the study during the consultation. In these patients, the investigators will perform OGM on the cytogenetic sample

Blood sample

Valentin Lestringant, MD

Hélène Guermouche Flament, MD

Dominique Penther, MD

Standard cytogenetics (CBA +/- FISH) is of diagnostic and prognostic interest in Ph- MPN. However, its value is limited by the low frequency of detected abnormalities. The development of tools to increase the sensitivity of detection of chromosomal alterations is therefore particularly adapted to these pathologies. Optical genome mapping (OGM) is a high resolution "long read" technique that allows the identification of structural and copy number variations at the whole genome level. Several recent studies suggest that OGM is a future tool for cytogenetic characterization of haematological disorders. Its ability to describe structural abnormalities, including balanced ones, represents a major advantage over currently used technologies. Thus, OGM seems to be the key tool for cytogenetics of haematological malignancies in the coming years, making it possible to replace, under certain conditions, not only karyotype and FISH, but CMA and even RT-MLPA for the search for fusion transcripts, thus filling in the gaps in these techniques while maintaining their advantages.

To define the place of this technology in Ph- MPN, the investigators will perform a OGM analysis on patients with Ph-MPN for whom bone marrow exploration is scheduled. These results will be compared with those of standard cytogenetics (CBA +/- FISH).

Evaluation of Optical Genome Mapping in Phi Negative Myeloproliferative Neoplasia in the Detection of Acquired Cytogenetic Abnormalities

Number of patients for whom the OGM finds at least the abnormalises detected by standard cytogenetics.

Hôpital Jeanne de Flandre LIlle

Centre Henri Becquerel

Centre Hospitalier Universitaire, Amiens

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer	NCT04716374	Epithelial Ovar...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)	NCT05839717	Myeloproliferat...	Blood sampling	18 Years -	University Hospital, Bordeaux
Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder	NCT00722254	Primary Myelofi... Primary Pulmona... Secondary Myelo... Pulmonary Arter...		18 Years -	University of Utah
Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder	NCT00722254	Primary Myelofi... Primary Pulmona... Secondary Myelo... Pulmonary Arter...		18 Years -	University of Utah
Evaluation of Optical Genome Mapping in Phi Negative Myeloproliferative Neoplasia in the Detection of Acquired Cytogenetic Abnormalities	NCT05714592	Myeloproliferat... Optical Genome ... Cytogenetics Clonality Prognostic Stra...	Blood sample	18 Years -	Centre Hospitalier Universitaire, Amiens

Spots Global Cancer Trial Database for clonality

Every month we try and update this database with for clonality cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for clonality

Every month we try and update this database with for clonality cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for clonality cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.