Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Aggression

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Lymphosarcoma

B-cell Lymphoma

All Drugs and Chemicals

Immunomodulating Agents

blood sample

Julie ABRAHAM, Dr

Danielle TROUTAUD, Pr

JULIE ABRAHAM, PH

Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Suboptimal response and/or resistance to rituximab have remained a challenge in the therapy of DLBCL but also of all B-NHL. Exosomes are microvesicles released from tumor B cells that are found in plasma of patients with B-NHL. Exosomes carry therapeutic targets (as CD20, PDL-1) and could act as "decoy-receptors" for immunotherapy. Our objective is to precise, in aggressive B-NHL, the role of exosomes in immunotherapy escape.

Diffuse large B-cell lymphomas (DLBCL) are highly aggressive and heterogeneous B-cell lymphoma that would imminently be fatal without treatment. Monoclonal anti-CD20 antibody, rituximab, in combination of CHOP chemotherapy (R-CHOP) is widely used with favourable results. Although more than half of patients achieve long-term remission, many are not cured with this immunotherapy. Decreased CD20 expression has been postulated to be one of the most important contributing to rituximab resistance. Moreover, R-CHOP therapies are sometimes ineffective, and new treatment strategies based notably on host immune responses modulation are being explored. Among them, programmed cell death ligand 1 (PD-L1) protein was identified as a potent predicting biomarker in DLBCL. Exosomes are small membrane vesicles secreted by several cell types during exocytic fusion of multivesicular bodies with the plasma membrane. Many cancer cells have been shown to secrete exosomes in greater amounts than normal cells. Exosome secretion may contribute to drug resistance. Indeed, exosome release from B-cell Non-Hodgkin Lymphoma (B-NHL), by the expression of CD20, has been suggest to act as decoy targets upon rituximab exposure, allowing lymphoma cells to escape from humoral immunotherapy. Finally, as exosome composition seems to be cell and tissue specific, they are highly suitable to serve as diagnostic markers.

Our hypothesis is that high expression of the immunotherapeutic targets (CD20, PD-L1) on exosomes derived from aggressive or resistant B-NHL may allow tumor cells to escape therapeutic antibodies, and thus contribute in vivo to therapeutic resistance. For this objective, we will used exosomes derived from DLBCL human cells and exosomes isolated from plasma of DLBCL patients. We will analyze, on these microvesicles, CD20 and PDL-1 expression in function of DLBCL sub-types and outcome of patients. Moreover, exosome capacity to interfere with immunotherapy will be also studied from in vitro and in vivo (xenografts) models.

Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas

Exosomes and Resistance to Immunotherapy in Aggressive Non-Hodgkin B-cell Lymphomas (B-NHL)

From D0 until the end of the inclusion period (36 months)

To analyze the prognostic value of exosomal markers on therapeutic response and patient outcome, each patient included in the study at diagnostic (D0) will be followed up until 36 months after inclusion.

University Hospital, Limoges

Hematologic Neoplasms

Lymphoma, Large B-Cell, Diffuse

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Everolimus

Rituximab

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Participants who received Everolimus 10 mg (two 5 mg tablets), daily for 12 months

Participants who received Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months

Everolimus was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.

Everolimus placebo was formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.

Everolimus Placebo

Novartis Pharmaceuticals

Phase III study of RAD001 adjuvant therapy in poor risk patients with Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 versus matching placebo after patients had achieved complete response with first-line rituximab-chemotherapy

Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy

A Randomized, Double-blind, Placebo-controlled, Multi-center Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

DFS was defined as the time from date of randomization to the date of event defined as the first documented relapse of the disease or death due to any cause. Relapse was based on investigator assessment and was assigned only if: It was documented according to Cheson guidelines by an objective radiological assessment method; It was documented by a biopsy proven lymphoma including new or recurrent bone marrow involvement; A new anticancer therapy for lymphoma started with subsequent confirmation of the relapse within 4 weeks of the start of this anticancer therapy

OS was defined as the time from date of randomization to date of death due to any cause. If the patient was not known to have died, survival was censored at the date of the last contact.

LSS was defined as time from randomization to death as a result of lymphoma.

RAD001 10 mg (two 5 mg tablets), daily for 12 months

RAD001 (Everolimus)

Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months

Placebo

All Patients in the Everolimus and Placebo groups.

All Patients

RAD001 (Everolimus)1

Total

Age, Continuous

Sex: Female, Male

Full Analysis Set (FAS) includes all randomized patients.

Study Director

Disease-free Survival (DFS)

2 years

3 years

4 years

5 years

6 years

Overall Survival (OS)

Lymphoma-specific Survival (LSS)

Overall Study

Infections

Symptoms and General Pathology

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Burkitt Lymphoma

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Amino Acids

Pirtobrutinib

Tyrosine Kinase Inhibitors

Tyrosine

Pirtobrutinib is an oral agent. LV20.19 CAR T cells will be administered either fresh or thawed after cryopreservation by IV injection.

Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion and restarted between day 28-120 for up to one year as maintenance post cell infusion.

Subjects will receive a dose of 2.5x10\^6 CAR-T cells/kg as a previously identified safe in a Phase 1 protocol at the Medical College of Wisconsin.

LV20.19 CAR T cells

Medical College of Wisconsin Cancer Center Clinical Trials Office

Nirav Shah, MD

This is a phase I, interventional, single arm, open label, treatment study designed to evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and maintenance in adult patients with B cell malignancies that have failed prior therapies.

This is the first study to evaluate the safety and impact of the combination of pirtobrutinib and LV20.19 CAR-T cells.

Pirtobrutinib is a first-in-class non-covalent Bruton's tyrosine kinase (BTK) inhibitor. The safe dose of this agent has been identified the BRUIN study as 200 mg daily administered as an oral agent. As a single agent, the toxicity profile has been favorable and does not overlap with other covalent BTK inhibitors with minimal cardiotoxicity and bleeding complications.

LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

Phase I Study of LV20.19 CAR T-cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5) occurring during the first 28 days following infusion.

Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).

Pirtobrutinib will be started again at 200 mg/day orally on day 28-120 for up to one year as maintenance post cell infusion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).

Medical College of Wisconsin

Associate Professor

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Participants with clinical diagnosis of GBM, that require dexamethasone due to neurological deficits. Dose is based on the clinical judgement of the treating physician but should be given at least two weeks. Dexamethasone is given once a day.

Participants with clinical diagnosis of GBM not requiring dexamethasone treatment.

The case group receives dexamethasone based on the clinical indication.

Mathilde CM Kouwenhoven, MD, PhD

Juan JJ Vallejo, PhD

Rationale: This project elaborates on a novel finding of the investigators that has not yet been reported in literature, namely the presence of elevated levels of atypical B cells in participants with glioblastoma. ln the period 2015 2018 the investigators analysed the blood immune subset composition of a cohort of 180 participants undergoing neurosurgery. The most relevant finding was the presence of an abnormally elevated level of B cells in the blood of the great majority of participants with glioblastoma. These B cells may be involved in the immunosuppression associated with glioblastoma that makes this tumor refractory to immunotherapy. Multiple regression analysis indicated that the increase in the frequency of atypical B cells in participants' peripheral blood was related with the administration of dexamethasone prior to surgery. However, this study design did not allow the investigators to address the causality of the relationship between dexamethasone and atypic B cell dysregulation. Alternative treatments to dexamethasone exist.

Objective: To investigate the effect of dexamethasone in the dysregulation of atypic B cells in participants with glioblastoma.

Study design: Observational case control pilot study with 20 participants (10 per group).

Study population: Newly diagnosed participants with glioblastoma. Intervention (if applicable): Observational study. Main study parameters/endpoints: Changes in the immune subset composition and functionality in the peripheral blood of participants with glioblastoma upon administration of dexamethasone for neurological signs of peritumoral edema (oral dexamethasone).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators will collect blood (28 ml) during the first visit and again (28 ml) at the time of surgery (2 weeks ± 3 days). There will not be additional site visits, physical examinations or any other tests, questionnaires. Blood collection is only a minor discomfort and it does not represent any additional risk.

Function and Composition of Regulatory B Cells in Participants With Glioblastoma

The Function and Composition of B Cells in Participants With Glioblastoma Treated With and Without Dexamethasone

Data will be stored in coded form in a Castor database. At this moment data will not be available to other researchers.

ldentify if dexamethasone treatment alters the frequency and functionality of atypic B cells (CD25+CD95Fas+-B cells) in blood in GBM.

Changes in the frequency and functionality of regulatory B cells in blood after two weeks of treatment with dexamethasone.

Changes in the frequency and functionality of regulatory B cells in blood in patients not treated with dexamethasone.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas	NCT03985696	Lymphoma, B-cel...	blood sample	18 Years -	University Hospital, Limoges
Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy	NCT00790036	Diffuse Large B...	Everolimus Everolimus Plac...	18 Years -	Novartis
LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies	NCT05990465	Non Hodgkin Lym... Diffuse Large B... Follicular Lymp... Marginal Zone L... Mantle Cell Lym... Burkitt Lymphom...	Pirtobrutinib LV20.19 CAR T c...	18 Years - 81 Years	Medical College of Wisconsin
Exosomes and Immunotherapy in Non-Hodgkin B-cell Lymphomas	NCT03985696	Lymphoma, B-cel...	blood sample	18 Years -	University Hospital, Limoges
Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy	NCT00790036	Diffuse Large B...	Everolimus Everolimus Plac...	18 Years -	Novartis
Function and Composition of Regulatory B Cells in Participants With Glioblastoma	NCT04128774	Glioblastoma, A...	Dexamethasone	18 Years -	Amsterdam UMC, location VUmc
Function and Composition of Regulatory B Cells in Participants With Glioblastoma	NCT04128774	Glioblastoma, A...	Dexamethasone	18 Years -	Amsterdam UMC, location VUmc

Spots Global Cancer Trial Database for b cells

Every month we try and update this database with for b cells 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 b cells

Every month we try and update this database with for b cells 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 b cells 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.