Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycoses

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Communicable Diseases

Bacterial Infections

Bacterial Infections and Mycoses

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

MT-101 preceded by conditioning (lymphodepleting) chemotherapy

MT-101

IV administration of fludarabine and cyclophosphamide

MT-101 + Conditioning (Lymphodepleting) Chemotherapy

Michele Gerber, MD, MPH

This is a Phase 1/2 study to test the safety, tolerability, and efficacy of the investigational agent MT-101 in patients with T cell Lymphoma. MT-101 is made with myeloid cells collected from the patient's blood. The myeloid cells are modified and later infused back into their veins. The modified myeloid cells recognize the tumor cells and are designed to target and kill them.

The research study is divided into two parts. The first part will be to determine the safety and tolerability of the study drug product. During this part of the study, there will be 4 groups of study patients. The first group of patients will receive a low dose of cells, the second group will receive the low dose of cells and lymphodepleting chemotherapy to reduce the number of T cells in the blood, the third group will receive a higher dose of cells, and the fourth group will receive the higher dose of cells and lymphodepleting chemotherapy to reduce the number of T cells in the blood. In the second part of the study, cells with or without chemotherapy will be administered based on results of Part 1 and the safety, tolerability, and efficacy of MT-101 will be assessed. All patient groups will receive 6 doses of drug product over 3 weeks.

A Study of MT-101 in Subjects With CD5+ Relapsed/Refractory TCL

A Phase 1/2, Open-Label, First-in-human, Multiple Ascending Dose Multicenter Study of MT-101 in Subjects With CD5+ Relapsed/Refractory T Cell Lymphoma

DOR is the time interval between the date of first assessment of PR or CR to the date of the follow-on first documentation of progressive disease or death, whichever occurs earlier.

PFS is defined as the time from the date of the first administration of MT-101 to the date of first documentation of progressive disease or death, whichever occurs earlier.

OS is defined as the time from date of the first administration of MT-101 to the date of death.

Safety and tolerability of the drug will be determined based on observed adverse events (AEs), including all potential dose limiting toxicities.

The ORR is defined as the number (%) of subjects achieving a best overall response of complete response (CR) or partial response (PR)

Myeloid Therapeutics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related 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

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Anti-Infective Agents

Interferons

Interferon-alpha

Subjects w/ovarian, primary peritoneal or fallopian tube ca who are not currently on therapy and are screening for trials, being seen in consultation, or presenting for enrollment on a trial.

Christina M Annunziata, M.D.

Background:

* Monocytes are a type of white blood cell found in human blood. They help the immune system. Researchers have found that monocytes taken from the blood of healthy people can kill tumor cells. Now they want to know if monocytes taken from the blood of people with ovarian cancer can kill tumor cells.
* In addition, native host anti-tumor cell mediated immune mechanisms may play a role in clinical outcome of epithelial ovarian cancer; data indicate that the presence of intra-tumoral CD3+ T-cells was shown to prognosticate improved outcome in advanced ovarian cancer. Furthermore, non-cellular components in the blood, such as exosomes, may influence outcome.

Objective:

- To see if monocytes taken from the blood of people with ovarian cancer can kill tumor cells.

Eligibility:

- Women 18 years and older with ovarian cancer.

Design:

* Participants will be screened with:
* Medical history and physical exam.
* Blood tests.
* CT scan of the chest, abdomen, and pelvis and/or an MRI. For these scans, they will lie in a machine that takes pictures of their body.
* A small amount of blood (two tubes) will be collected by needle during one visit.

Background:

Using both in vitro and in vivo assays we have shown that human monocytes primed with Interferons alpha and gamma are tumoricidal and are capable of killing a number of tumor cell lines and human tumors implanted into immunocompromised mice. We have shown that monocytes isolated through elutriation at the NIH blood bank and monocytes isolated from anticoagulated peripheral blood from healthy women from the NIH blood bank are equally capable of killing tumor cells. No data have been collected as to whether monocytes from patients with Ovarian, Primary Peritoneal, or Fallopian Tube Cancer have tumoricidal properties. In addition, native host anti-tumor cell mediated immune mechanisms may play a role in clinical outcome of epithelial ovarian cancer; data indicate that the presence of intra-tumoral CD3+ T-cells was shown to prognosticate improved outcome in advanced ovarian cancer. Furthermore, noncellular components in the blood, such as exosomes, may influence outcome.

Objectives:

To obtain blood samples from patients with ovarian, primary peritoneal or fallopian tube cancer.

Eligibility:

Females greater than or equal to 18 years of age with a prior diagnosis of ovarian, primary peritoneal or fallopian tube cancer seen in the Women s Cancer Clinic of the NCI. Patients must be able and willing to provide informed consent.

Design:

We will collect approximately 20 ml of peripheral blood at a single time point from patients with ovarian, primary peritoneal or fallopian tube cancer who are not currently on therapy and are screening for trials, being seen in consultation, or presenting for enrollment on a clinical trial.

Blood Collection From People With Ovarian Cancer

Collection of Blood From Patients With Ovarian, Primary Peritoneal or Fallopian Tube Cancer

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

A collection of blood samples from patients with ovarian, primary peritoneal or fallopian tube cancer

National Cancer Institute (NCI)

Hypoxia

Necrosis

Shock, Septic

Shock

Sepsis

Toxemia

Syndrome

Systemic Inflammatory Response Syndrome

Inflammation

30 Adult patients (age \> 18years), with severe sepsis or septic shock as defined by the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference guidelines at the time of admission to ICU.

Blood samples will be taken at ICU admission, and 24h and 48h after admission, and at time of resolution of sepsis

blood sampling

Blood samples will be taken twice at a 7 day interval

Tobias Merz

Introduction: Evidence suggests that sepsis and septic shock severely impair mitochondria and that the resulting mitochondrial dysfunction is related to the severity and outcome of the resulting organ dysfunction. In sepsis mitochondrial abnormalities - biochemical and ultrastructural - have been recognized in multiple organs, including liver, kidney, skeletal and heart muscle tissue and blood cells. Circulating immune cells play an important role in the pathophysiology of sepsis. Stimulation of the immune system alters the energy requirements of immune cells; down-regulation of immune-cell activity has been associated with prolonged sepsis and unfavourable outcome. The aim of the project is to comprehensively investigate changes in mitochondrial function of immune cells in patients with severe sepsis and septic shock. The following main hypotheses will be evaluated:

* Severe sepsis and septic shock leads to increased energy requirements of immune cells and to an increase in mitochondrial enzyme activities and energy production.
* Changes of mitochondrial function in human immune cells are associated with alterations in clinical and laboratory markers of severity of sepsis.
* Prolonged sepsis and unfavourable outcome is associated with down regulation of mitochondrial function.

Methods: A total of 30 adult patients admitted to the intensive care unit (ICU) due to severe sepsis or septic shock will be included in the study; 30 healthy volunteers serve as controls. Patients with any type of chronic infectious, inflammatory or autoimmune diseases, after transplantations or receiving immunosuppressive agents are excluded.

Collected baseline characteristics include patient demographics, diagnosis and severity of illness scores at the time of admission. Daily collected follow up data include clinical and laboratory parameters of organ dysfunction, use of vasopressors/inotropes, use of antibiotics, use of steroids and results of microbiological cultures/stains.

Negative identification and isolation of monocytes, B cells and CD4 T cells will be performed daily from ICU admission to discharge using an antibody-antigen mediated immunomagnetic cell isolation procedure that depletes all blood cells except the specific target cells. Mitochondrial function of immune cells will be assessed by measurement of mitochondrial complex activity for complexes I to IV by a standard titration protocol. Additionally, the levels of pro- and anti-inflammatory cytokines (Interleukin (IL)-1, IL-6, IL-10, TNF-α) will be assessed throughout the stay in the ICU. For comparison mitochondrial function of of monocytes, B cells and CD4 T cells and cytokine levels will be measured in a group of 10 healthy volunteers.

Analysis plan: Changes in mitochondrial function of immune cells over time compared to a healthy control group and during the course of severe sepsis and septic shock is the main outcome parameter of this study. Assessed predictors are determined by the severity of the underlying septic condition and include clinical and laboratory evidence for dysfunction of vital organ systems and changes in levels of inflammatory and anti-inflammatory cytokines.

Background

Evidence suggests that sepsis and septic shock severely impair mitochondria and that the resulting mitochondrial dysfunction is related to the severity and outcome of the resulting organ dysfunction. In sepsis mitochondrial abnormalities - biochemical and ultrastructural - have been recognized in multiple organs, including liver, kidney, skeletal and heart muscle tissue and blood cells. A systematic review on mitochondrial function assessed as oxygen consumption, state 3 and state 4 respiration, respiratory enzyme activity, or tissue ATP levels and turnover rates showed decreased function especially in sepsis models lasting more than 16h . Depleted levels of reduced glutathione, an important intra-mitochondrial antioxidant, in combination with increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) inhibit oxidative phosphorylation and ATP generation. This acquired intrinsic derangement in cellular energy metabolism contributes to reduced activities of mitochondrial electron transport chain enzyme complexes and impaired ATP biosynthesis and contributes to the organ dysfunction in sepsis.

Circulating immune cells play an important role in the pathophysiology of sepsis. Stimulation of the immune system alters the energy requirements of immune cells; down-regulation of immune-cell activity has been associated with prolonged sepsis. Immune cell activation mandates an increase in energy requirements, thus a reduced production of ATP due to impaired mitochondrial function may be a factor in modulating the immune response in sepsis. Alterations in mitochondrial function and energetic failure have been reported in peripheral blood mononuclear cells and seem to be associated with the modulation of the immune response to sepsis. Macrophages incubated with endotoxin/interferon-γ show a decrease in oxygen consumption and inhibition of mitochondrial I complex. Different mechanisms for alteration of mitochondrial function in these cells have been proposed, including increases in NO production and nitration of mitochondrial proteins \[14\], elevation of IL-10 \[15\] or prostaglandin levels. In human neutrophils intact mitochondrial function plays an important role in chemotaxis and phagocytosis, impairment of these mechanisms leads to a decreased defence ability to microbial challenges.

HIF-1α is a transcription factor that acts as a key regulatory factor in the evolution of oxygen homeostasis. Under normoxic conditions HIF-1α is continuously synthesized and degraded after hydroxylation by dioxygenases that utilize oxygen, Fe and α-ketoglutarate as substrates. During hypoxia, the low availability of oxygen limits the reaction; HIF-1α is no longer degraded and rapidly accumulates and triggers the transcription of genes involved in oxygen homeostasis such as glycolytic enzymes, glucose transporters, vascular endothelial growth factor (VEGF) and erythropoietin. Under hypoxic conditions, HIF mediates also a decrease in mRNA levels of the respiratory chain proteins, preparing the cell to produce ATP mainly from glycolysis and not from oxidative phosphorylation, thereby optimizing cell energetics and homeostasis for survival and function during hypoxia.

Recent published reports have linked inflammation and endotoxin stimulation to HIF-1α activation. HIF-1α has been shown to be up-regulated and stabilized in LPS-treated macrophages and monocytes under normoxic conditions. HIF-1α levels were shown to be decreased in macrophages deficient in TLR4 after LPS stimulation, suggesting that LPS stimulation of HIF-1α is mediated by TLR4.

Data on mitochondrial function of human immune cells in severe sepsis is limited and the potential correlation of mitochondrial energy requirements and production and the severity of the patient's condition and outcome are not well established. The immunologic reaction in the context of severe sepsis and septic shock consists of an interdependent, highly complex system that involves different types of immune cells and pro- and anti-inflammatory cytokines involved in a time-dependent process. Simple in-vitro studies assessing mitochondrial function of a single type of immune cells and single cytokines just a one point in time during the course of the septic process might not be an appropriate model to mirror the complex interactions of the immune system. Serial measurements of mitochondrial function of different key-player cells and specific pro- and anti-inflammatory cytokines and apoptosis markers parallel with other clinical and laboratory markers of sepsis may offer a more in-depth evaluation and understanding of this deleterious disease pattern.

Objective

The aim of the project is to comprehensively investigate changes in mitochondrial function and morphology of immune cells in patients with severe sepsis and septic shock. We plan to assess changes in mitochondrial function of monocytes, B cells and CD4+ T cells in correlation to levels of various cytokines and to classic clinical and laboratory parameters of severity of sepsis and outcome.

Methods

A total of 30 patients admitted to the intensive care unit (ICU) of a tertiary care hospital due to severe sepsis or septic shock will be included in the study after obtaining written informed consent of the patient or the patient's next of kin. Patients with any type of chronic infectious, inflammatory or autoimmune diseases, after transplantations or receiving immunosuppressive agents are excluded.

Controls: 30 healthy volunteers Assessment of mitochondrial function of monocytes/granulocytes will be performed by measurement of mitochondrial complex activity using a standard titration protocol to measure activation of complex I to IV. To measure serum levels of IL-1, IL-6, IL-10 and TNF standard commercial kits will be used.

Serum, isolated B-cells, T-cells, Monocytes

Mitochondrial Function of Immune Cells in Sepsis

Mitochondrial Function of Immune Cells in Severe Sepsis and Septic Shock - a Prospective Observational Cohort Study

Insel Gruppe AG, University Hospital Bern

Neoplasm Metastasis

Adrenal Insufficiency

Addison Disease

Neoplastic Processes

Adrenal Gland Diseases

Autoimmune Diseases

Addison's Disease

Secondary Adrenal Insufficiency

Anti-Inflammatory Agents

Vasoconstrictor Agents

Respiratory System Agents

Dermatologic Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Epinephrine

Glucocorticoids

Cortisone

Racepinephrine

Epinephryl borate

Hydrocortisone-17-butyrate

Hormones

Hormone Antagonists

Plenadren (modified release hydrocortison) 20-25 or 30 mg oral tablets will be administered once-daily at 8.00 AM in the fasting state The dose is kept the same as patients had before entering the trial.

Hydrocortisone (dose range 10 to 30) mg will be continued as before entering the study. Cortisone Acetate (dose 25 to 37.5 mg) will be continued as before entering the study. The morning dose will be administered in the fasting state.

The total daily dose and timing is not changed during the study period.

Healthy volunteers will be enrolled as control group

Plenadren

Conventional glucocorticoid therapy

Andrea M Isidori, MD, PhD

This is a randomized, controlled, open, three-armed, multi-centre study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on anthropometric parameters, metabolic syndrome, infectious, immunological profile, cardiovascular system, bone mass and quality of life in patients affected by primary or secondary adrenal insufficiency.

Hypocortisolism is a disease with more than 80% 1-year mortality before the availability of synthetic glucocorticoids. Current replacement therapy has improved this dramatically, but recent data suggest that outcome is still compromised. Patient receiving conventional glucocorticoids therapy have compromised quality of life, reduced bone mass, increased risk factors for cardiovascular disease, infectious, tumors and premature mortality that is more than twice the mortality rate in the background population. Circulating cortisol levels follow a distinct diurnal pattern with high levels in the early morning and low trough values around midnight. Using available formulations for replacement therapy this circadian rhythm is had to mimic and also during the active time of the day high peaks and low troughs occur.

In this trial a dual-release hydrocortisone preparations that has in healthy volunteers been able to mimic the circadian pattern of circulating cortisol was studied in patients with primary and secondary adrenal insufficiency.

Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM)

A Randomized, Controlled, Multi-Centre Trial on the Effects of Dual-release Hydrocortisone Preparations Versus Conventional Glucocorticoid Replacement Therapy in Patients Affected by Primary and Secondary Adrenal Insufficiency. DREAM Trial.

Single outcome measurement of body weight (kg).

Composite outcome measure consisting of simultaneous measurment of: Glycaemia, Insulinemia, Homa index, Glycated Haemoglobin, Total Cholesterol, LDL cholesterol, HDL cholesterol, Triglyceredes; the composite outcome measured at 3 and 6 months.

Composite outcome measure consisting of simultaneous measurment of: Full Count Blood Cell, ESR, Fibrinogen, Immunoglobulin, PCR; measured at baseline, 3 and 6 months.

Composite outcome measure consisting of simultaneous measurment of: serum calcium, phosphate, parathyroid hormone (PTH), 25OH-vitamin D, phosphate, osteocalcin, bone phosphate alkaline (sBALP), serum-cross-linked N and C-telopeptide of bone type I collagen (NTx- CTx); measure at baseline and 6 months.

Measurement of epicardial fat thickness (EFT) by hihg-resolution M-B-mode transthoracic echocardiography from baseline at 6 months.

Evaluation of hepatic steatosis by conventional ultrasound of the liver and with ASQ software with dedicated equipment and 7-5 Mhz convex probe frome baseline at 6 months.

Quality of life will be measured by questionnaires: AddiQol, Middle Sex Hospital Questionnaire (MHQ), International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), Beck Depression Inventory Test (BDI-II).

Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)

University of Roma La Sapienza

Professor

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Analgesics

Vaccines

Aldesleukin

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Analgesics, Non-Narcotic

Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m\^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10\^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over 15 minute period every 8-hours for up to 14 doses.

Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m\^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10\^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over 15 minute period every 8-hours for up to 14 doses. After completion of the IL-2 treatment 3-5 doses of weekly intradermal vaccinations with up to 1.5 x 10\^7 Dendritic cells pulsed with autologous tumor lysate and NY-ESO-1 peptide.

T cells

Dendritic cell vaccine

Maria Wolodarski, MD

Rolf Kiessling, MD, PhD

The purpose of this study is to learn if dendritic cell vaccine will increase the effect of tumor infiltrating lymphocytes given with chemotherapy and interleukin-2 in patients with melanoma.

The MAT02 clinical trial is a phase 1 clinical trial with the objective to assess the safety, feasibility and immunological efficacy of the combined application of two immunological treatment modalities in patients with metastatic melanoma:

1. Cohort A: After a non-myeloablative conditioning regimen, 5 patients will receive one bulk infusion of T cells. T cells will be expanded ex vivo from autologous tumor infiltrating lymphocytes (TIL). In vivo persistence of the infused cells will be supported by administration of IL-2, a T cell survival factor.
2. Cohort B: This adoptive cell transfer (ACT) step will in additional 10 patients be followed by a vaccination with autologous, in vitro-generated, dendritic cells (DC), loaded with autologous tumor lysate and a synthetically produced peptide derived from the tumor associated antigen NY-ESO 1.

T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma

A Phase I Study to Evaluate Safety, Feasibility and Immunologic Response of Adoptive T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Metastatic Melanoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of MT-101 in Subjects With CD5+ Relapsed/Refractory TCL	NCT05138458	Lymphoma, T-Cel... Lymphoma, T-Cel... Mycosis Fungoid... Adoptive Cellul... Cell Therapy	MT-101 MT-101 + Condit...	18 Years -	Myeloid Therapeutics
Blood Collection From People With Ovarian Cancer	NCT02063464	Ovarian Cancer Cancer of the O... Ovarian Neoplas...		18 Years -	National Institutes of Health Clinical Center (CC)
Mitochondrial Function of Immune Cells in Sepsis	NCT01600989	Shock, Septic	blood sampling blood sampling	18 Years -	Insel Gruppe AG, University Hospital Bern
Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM)	NCT02277587	Primary Adrenal... Secondary Adren...	Plenadren Conventional gl...	18 Years - 80 Years	University of Roma La Sapienza
Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM)	NCT02277587	Primary Adrenal... Secondary Adren...	Plenadren Conventional gl...	18 Years - 80 Years	University of Roma La Sapienza
Mitochondrial Function of Immune Cells in Sepsis	NCT01600989	Shock, Septic	blood sampling blood sampling	18 Years -	Insel Gruppe AG, University Hospital Bern
A Study of MT-101 in Subjects With CD5+ Relapsed/Refractory TCL	NCT05138458	Lymphoma, T-Cel... Lymphoma, T-Cel... Mycosis Fungoid... Adoptive Cellul... Cell Therapy	MT-101 MT-101 + Condit...	18 Years -	Myeloid Therapeutics
T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma	NCT01946373	Melanoma	Cyclophosphamid... Fludarabine T cells Interleukin-2 Dendritic cell ...	18 Years - 74 Years	Karolinska University Hospital

Spots Global Cancer Trial Database for monocytes

Every month we try and update this database with for monocytes 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 monocytes

Every month we try and update this database with for monocytes 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 monocytes 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.