Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

15 patients with DLBCL with chemoresistance or relapsed less than 2 years after completion of first-line therapy

15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line therapy.

Large-cell B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and accounts for about 40% of new cases. Although the DLBCL is a single entity in the WHO classification, several subgroups with different prognoses are recognized. These subgroups take into account the tumor localization (primitive cerebral lymphoma, serous lymphoma, intravascular or exclusive lymph node) or a particular molecular signature (GCB profile, germline center B cell or ABC, activated B cell). Despite the introduction of immunotherapy, treatment failures are common. Overall survival at 5 years is estimated to be between 26 and 73%. This highlights the important heterogeneity of this pathology and therefore the need for biomarkers prognosis. Recently, an increase in monocytes in the blood of DLBCL patients has been proposed as a prognostic factor for independent survival. This marker of poor prognosis is also found in many solid.

Monocytes are effectors of the inflammatory response. They have different functional profiles depending on the level of expression of CD14 and CD16. Four subtypes of monocytes are distinguished: classical (CD14posCD16neg), intermediate (CD14posCD16pos) and non-classical (CD14lowCD16pos); the latter population is divided into two sub-groups depending on the expression of the SLAN protein. The different monocytic subpopulations have very diverse functions ranging from an immunosuppressive profile to an activation of the immune system. CD14posCD16neg monocytes are specialized in phagocytosis, production of oxygen derivatives (ROS) and pro-inflammatory cytokine secretion in response to microbial infection. CD14dimCD16pos monocytes are specialized in immune surveillance and produce proinflammatory cytokines such as TNFα and IL-1β in response to LPS stimulation.7 The Slanpos subpopulation produces IL-12 and thus has pro-inflammatory properties. Finally, CD14posCD16pos monocytes have controversial functions. For some authors, they produce the immunomodulatory cytokine IL-10, inhibit the proliferation of CD4 T lymphocytes and induce the recruitment of regulatory T lymphocytes, while for others they produce TNF-α, a pro- inflammatory.From a practical point of view CD14 and CD16 expression forms a continuum, which translates into complexity in the phenotypic definition of these cells and explains the contradictory data on their functionalities. Interestingly, in a laboratory work and in the course of publication, this fraction is increased in the blood of DLBCL patients compared to healthy donors (manuscript in preparation), on the contrary the monocytic fraction CD14dimCD16 pos is decreased in these patients.

In the end, if the increase in monocytes is known to be poor prognosis in patients with DLBCL, the monocyte fraction involved and the monocytic functions involved in this phenomenon are not known.

Since 2011, the Clinical and Biological Hematology Services have a database from a research protocol (BMS_LyTrans). This protocol includes patients with DLBCL as well as healthy patients, in order to allow the biological characterization of biomarkers in this pathology. Thus, we have blood samples and analysis of certain monocyte subtypes by flow cytometry at diagnosis, in more than 100 patients with DLBCL.

Primary objective :

Describe and compare the distribution of the different monocytic subpopulations according to the chemosensitivity profile (group 1) or chemoresistance (group 2) of patients with DLBCL and healthy donors (group 3), and identify their specific functionalities.

Secondary objective :

To determine the prognostic impact in terms of progression-free survival (EFS) of the distribution of the monocytic sub-population (s) defined i during the primary objective, in a retrospective study (BMS Ly Trans)

Design/Methodology : Retrospective, observational, monocentric study.

1. - Part 1: Phenotypic and functional study of monocytic sub - populations of patients with DLBCL.

   - Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy.

   Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment.

   Group 3: 15 healthy patients.

   A - Irish Lab (Nashville)

   - Phenotypic analysis by mass cytometry: This new technology allows the integration of multiple data with membrane markers, intracytoplasmic proteins as well as transcription factors, thus providing global modeling of signaling pathways

   B - UMR 917 (Rennes) 8 months Cell sorting: The four subtypes of monocytes described above will be sorted by flow cytometry according to the expression of CD14, CD16 and Slan.

   - High-throughput transcriptional analysis: cell lysis and real-time PCR in order to study the expression of genes involved in the mechanisms of immunomodulation.Bio-informatics, Integrated analysis: The set of clinical, transcriptomic and proteomic data will be analyzed in an integrated way using tools and algorithms working within the Irish lab.
2. - 2nd part (Rennes) - 6 months : Populations differentially expressed between groups in part 1 will be analyzed on a cohort of 100 samples. These parameters will be analyzed jointly after integration in a database, uni- and multivariate analysis and the survival probability will be calculated for groups with a log-rank test.

Expected benefits :

1. - To allow a better understanding of the monocyte compartment in DLBCL, particularly with regard to the immunosuppressive capacity of some of these cellular subtypes.
2. - To refine the interest of the biomarker "monocyte level" on EFS in patients with DLBCL, highlighting the monocyte subtype involved.
3. - To continue the collaboration between the two sites, which will allow to combine technologies and expertise present in Rennes (patient recruitment, cell sorting, molecular analysis (Biomark)) or in Nashville (CyTOF, bioinformatics, integrated analysis).

Patient selection from the BMS_LyTrans database

SMOLY : Phenotype and Functions of Monocyte Subtypes in High Grade B Lymphoma: Towards New Biomarkers?

Increased proportion of one or more monocytic sub-populations (s) and / or modulation of the markers tested in one of the three groups studied.

Difference of EFS in the validation cohort between patients with DLBCL having an increased proportion of one or more monocytic subpopulation (s) or modulation of the markers suspected in the descriptive phase, and the others.

Vanderbilt University

Rennes University Hospital

Digestive System Diseases

Gland and Hormone Related Diseases

Carcinoma

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

taking blood samples from healthy people

Macrophages are derived from monocytes recruited to the tumor site and stimulated by specific chemokines secreted by tumor cells. These tumor associated macrophages (TAMs) have been postulated as being involved in the progression of cancer.

Based on our preliminary findings and on published data we hypothesized that macrophage-induced chemoresistance (MIC) can promote survival of pancreatic carcinoma cells during chemotherapy.

The overall goal of this study is to evaluate the mechanism of MIC in an in-vitro model of Pancreatic ductal adenocarcinoma (PDA).

methods:

1. The human PDA cell line Panc1 will be grown in suitable conditions.
2. Macrophages will be produced by incubating mononuclear cells from the blood of healthy donors in medium with M-CSF for 7 days.
3. TAMs will be generated by culturing these macrophages with tumor-culture conditioning medium (TCCM) of PDA Cells for an additional 72 hours.
4. Human pancreatic cells (PANC1) will be treated with gemcitabine following exposure to macrophages CM.
5. Cell proliferation will be quantified by light microscopy and by an XTT Cell Proliferation Assay Kit.

Macrophages Effect on Chemoresistance

Impact of Macrophages on De-Novo Chemoresistance of Adenocarcinoma Cells

the macrophages will be isolated from the blood we'll get from the healthy volunteers. the outcome measure is related to the basic research and not clinical so there's no symptom/outcome related to the participants.

Rambam Health Care Campus

MD PhD student

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Annika Auranen, adj prof

Epithelial ovarian cancer is the most lethal gynecological malignancy in developed countries and the fifth most common cause of cancer-related death in women. Poor prognosis is due to challenges in early diagnosis and development of inevitable resistance to chemotherapy in majority of patients despite of good initial treatment response. The purpose of this prospective study is to analyze variation in microRNA expression in prediction of primary treatment response and the role of microRNAs in development of chemoresistance in epithelial ovarian cancer.

• Objectives: To screen microRNAs from prospectively collected plasma, urine and tumor samples from patients diagnosed with epithelial ovarian cancer. Samples are analyzed for microRNA expression and differential expression is correlated with primary treatment response, progression-free survival and overall survival.

• Methods: Plasma, urine and tumor samples are collected at primary surgery (open surgery or diagnostic laparoscopy) or interval debulking surgery, at 1st, 3rd and 6th neoadjuvant or adjuvant chemotherapy and at progression for high-throughput screening of microRNA expression by array technology.

Inclusion criteria:

patients operated for a suspected ovarian malignancy in the Department of Obstetrics and Gynecology in Tampere University Informed consent obtained

Molecular Mechanisms Leading to Chemoresistance in Epithelial Ovarian Cancer

Expression profile calculated with bioinformatical analysis

Tampere University

University of Helsinki

Tampere University Hospital

Chief in gynecological oncology

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites, for whom neoadjuvant chemotherapy is recommended.

Patients will receive neoadjuvant chemotherapy according to ESGO guidelines

Borut Kobal, MD; PhD

Katarina Černe, MD, PhD

Ovarian cancer has the highest mortality rate among all gynecologic cancers, with most patients presenting with advanced stage tumors. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time up to 80 % of others develop chemoresistance, rendering recurrent disease incurable. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The aim of the study is to demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin.

RATIONALE:

Recent studies suggest that the copper efflux transporters ATP7A plays an important role in platinum resistance. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The literature concludes that new methods are required to detect resistant tumor cells at an early chemotherapy stage and suitably adapt treatment. There is still much uncertainty regarding how the fate of platinum compounds in a cell follows the regulatory copper pathways, especially during transport from the cell. The question is also to what extent these processes are cell-specific, especially because experiments to date regarding the role of ATP7A in resistance to platinum compounds have been conducted on nonserous cell lines (especially of the endometrioid histological type).

AIM OF THE STUDY:

Study will evaluate the ATP7A transporter as an important mediator of chemoresistance to platinum compounds to obtain an additional criterion for the optimal treatment strategy for serous ovarian cancer patients. The focus will primarily be on intrinsic chemoresistance, which determines the initial response to chemotherapy. Research to date has failed to evaluate the influence of ATP7A transporter expression solely on serous ovarian cancer.

The study will demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin. Because the measurement of ATP7A in bodily fluids is unreliable, the plan is to measure ceruloplasmin in the patients' ascites. Ceruloplasmin is the main copper-transporting protein in the blood. It is synthesized in the cell and, according to findings in the literature, it is ATP7A that is responsible for delivering copper to ceruloplasmin. When copper binds to ceruloplasmin, there is no other way for it to cross the plasma membrane than via the ATP7A transporter. By measuring the ceruloplasmin level in the ascites, ATP7A activity or its localization on the plasma membrane could indirectly be measured as well. To confirm the suitable measurement of ceruloplasmin in the ascites, its values in the patients' blood plasma and tissue will be measured.

METHODS:prospective clinical trial It will include 30 high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites. The patients will be presented to the gynecological-oncological consultation team at the Ljubljana Division of Gynecology and Obstetrics. Patients for whom neoadjuvant chemotherapy is recommended will be included in the trial.

STATISTICAL ANALYSES: The normality of numerical variables' distribution will be tested with the Shapiro-Wilk test. Relevant parametric tests (Student's t-test) or nonparametric tests (the two-tailed Mann-Whitney U-test) will be used to compare groups.

Role of the ATP7A Transporter in Ovarian Cancer

ATP7A Transporter as Biomarker for Predicting Chemoresistance of Serous Ovarian Cancer

To measure concentration of ceruloplasmin in blood and ascites

To measure concentration of ceruloplasmin after three to six chemotherapy cycles

To measure expresion of ATP7A after three-six cycles of chemotherapy

University of Ljubljana, Faculty of Medicine, Institute of Pharmacology and Experimental Toxicology

University Medical Centre Ljubljana

Asist. David Lukanovic, MD

Symptoms and General Pathology

Infections

Recurrence

Virus Diseases

Adenocarcinoma, Clear Cell

Vaccinia

Adenomyoepithelioma

Fallopian Tube Neoplasms

Fallopian Tube Diseases

Fallopian Tube Cancer

Epithelial-myoepithelial Carcinoma

Anti-Infective Agents

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Bevacizumab

Doxorubicin

Liposomal doxorubicin

Cisplatin

Immunomodulating Agents

Taxane

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0

Platinum-doublet \& bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5

Physician's Choice of chemotherapy \& bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).

Olvi-Vec is an engineered oncolytic vaccinia virus

olvimulogene nanivacirepvec

Platinum chemotherapy: carboplatin (preferred) or cisplatin

Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin

Bevacizumab (or biosimilar)

Stefanie White

Jennifer M Scalici, MD

Claudia Al Khairi

Setsuko K. Chambers, MD

Edward Wang, MD, PhD

Alexandrea Cronin

Michael McHale, MD

Ramez Eskander, MD

Esmeralda Martinez

Alberto Mendivil, MD

Krishnansu S. Tewari, MD

Karla Hernandez-Cruz

Robert W Holloway, MD

Monica Rengifo Pardo, MD

Matthew L. Anderson, MD, PhD

Megan Indermaur, MD

Rebekah Little, CRC

Cheri West, RN

Jessica E. Parker, MD

Lyudmila Igorevna Kalnitskaya, MBA, MS

James F Barter, MD

Robert Morris, MD

Linda Odibo

Premal Thaker, MD

Crystal Tindall, BSN, RN

Jessica Black

Dan-Arin Silasi, MD

Peter Lim, MD

Leah Wilson

Erin K Crane, MD

Jackie Ludwig

Peter Rose, MD

Daniel Geyer

Tammy Bonham

Thomas J. Reid, MD

Debra Richardson, MD

Ashma Acharya

Sarah Crafton, MD

Crystal Knox

Whitney S Graybill, MD

Stephen DePasquale, MD

Kim Donelson, LPN CCRP

Jodie Mactagone, CRC

Melanie Bergman, MD

The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant/refractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.

Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1, laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy. This study is to test the hypothesis that the combination of Olvi-Vec followed by further chemotherapy is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participant population includes histologically confirmed non-resectable platinum-resistant/refractory ovarian cancer (PRROC). Determination of progression-free survival, safety and overall survival are key objectives. Participants randomized into the Experimental Arm will receive a single-cycle (2 infusions on two consecutive days) of Olvi-Vec through an intraperitoneal catheter. The catheter is then removed, and patients receive systemically administered platinum-doublet chemotherapy and bevacizumab. The control arm receives the Physician's Choice of chemotherapy and bevacizumab at the same dose and schedule. Biological samples will be obtained from some Experimental Arm participants for virus-shedding testing. Assessment of response to treatment in both arms will be by RECIST 1.1 and iRECIST as assessed by Blinded Independent Central Review. Maintenance/continued treatment with non-platinum chemotherapy and bevacizumab is dependent on a participant being clinically stable until confirmed progressive disease by iRECIST or can no longer tolerate therapy.

Dr. Robert W. Holloway (AdventHealth Cancer Institute, Orlando, FL) will serve as the National Principal Investigator for this Phase 3 study in PRROC.

Randomization (2:1) is either into the Experimental Arm which is Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or into the Active Comparator Arm which is Physician's Choice of chemotherapy and bevacizumab.

Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)

A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Physician's Choice of Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)

To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.

Determine safety and tolerability of administering multiple doses of Olvi-Vec via intraperitoneal catheter in combination with platinum-doublet and bevacizumab (or biosimilar) as assessed by CTCAE v. 5.0 following initiation of study treatment until end of study participation.

Time from date of first response until the first date of progressive disease based on radiological assessment.

Time from randomization to first documented disease progression based on radiological assessment or death from any cause.

Time from randomization to first documented disease progression with confirmatory imaging scan performed 4-8 weeks after unconfirmed disease progression or death from any cause.

Ratio of the sum of CR \& PR divided by the number of ITT participants from start of treatment to confirmation of response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SMOLY : Phenotype and Functions of Monocyte Subtypes in High Grade B Lymphoma: Towards New Biomarkers?	NCT03672682	DLBCL		18 Years - 70 Years	Rennes University Hospital
Macrophages Effect on Chemoresistance	NCT01921699	the Focus of th...	taking blood sa...	18 Years - 40 Years	Rambam Health Care Campus
Molecular Mechanisms Leading to Chemoresistance in Epithelial Ovarian Cancer	NCT02758652	Ovarian Cancer		18 Years -	Tampere University Hospital
Role of the ATP7A Transporter in Ovarian Cancer	NCT05490407	Gynecologic Can... Ovarian Cancer High Grade Sero... Chemotherapy Ef...	Carboplatin	18 Years - 80 Years	University Medical Centre Ljubljana
Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)	NCT05281471	Platinum-resist... Platinum-refrac... Fallopian Tube ... Primary Periton... High-grade Sero... Endometrioid Ov... Ovarian Clear C...	olvimulogene na... Platinum chemot... Non-platinum ch... Bevacizumab (or...	18 Years -	Genelux Corporation
9-ING-41 in Patients With Advanced Cancers	NCT03678883	Cancer Pancreatic Canc... Sarcoma Renal Cancer Refractory Canc... Refractory Neop... Refractory Non-... Pancreatic Aden... Resistant Cance... Neoplasm Metast... Neoplasm of Bon... Neoplasm, Breas... Neoplasm of Lun... Neoplasms,Color... Neoplasms Pancr... Malignant Gliom... Malignancies Malignancies Mu... Bone Metastases Bone Neoplasm Bone Cancer Pancreas Cancer Pancreatic Neop... Breast Neoplasm... Acute T Cell Le...	9-ING-41 Gemcitabine - 2... Doxorubicin. Lomustine Carboplatin. Nab paclitaxel. Paclitaxel. Gemcitabine - 2... Irinotecan	18 Years -	Actuate Therapeutics Inc.
Prediction of the Response to Chemotherapy by Tomoscintigraphie the MIBI in the Balance Sheet Pre Hodgkin's Disease and Lymphoma Malins High Grade	NCT00551798	Hodgkin's Disea... Malignant Lymph... Chemoresistance	TEP au MIBI	18 Years -	University Hospital, Limoges

Spots Global Cancer Trial Database for chemoresistance