Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasms

Hyperplasia

Endometrial Hyperplasia

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

All Drugs and Chemicals

Estrogens

Progesterone

pathology according to histological examination

Participants investigated the expression level of estrogen and progesterone receptors (ERα, ERβ, GPER, PRA, PRB, mPR, PGRmC1) by RT-PCR in pathological endometrial tissue and peripheral blood mononuclear cells. GABDH was used as a comparison gene.

endometrial tissue and peripheral blood mononuclear cells receptivity

Dina Gutorova, PhD

A prospective observational study of endometrial tissue and peripheral blood mononuclear cells receptivity to sex steroid hormones in postmenopausal patients with endometrial proliferative processes

Endometrial cancer is in third place among cancer diseases in female population of Russia. The peak morbidity occurs during the postmenopausal period. In this regard, early diagnosis of previous endometrial proliferative processes and effective methods for their treatment are relevant. However, failures with hormonal therapy are often observed. This may be due to the low receptivity of the pathological tissue. It is also known that the functional activity of immunocompetent cells is controlled by the immune system, however, studies of the receptivity of peripheral blood mononuclear cells to sex steroid hormones were carried out in healthy blood donors. Changes in mononuclear cells receptivity may be one of the pathogenetic links in the development of endometrial proliferative processes and endometrial cancer. This may also influence the effectiveness of their treatment. In this regard, the purpose of the study is to evaluate the role of the expression of estradiol and progesterone receptor genes in endometrial tissue and peripheral blood mononuclear cells in the occurrence of endometrial proliferative processes in postmenopausal patients with a pathogenetic justification for the choice of treatment method. To achieve this goal, the investigators investigated the expression level of estrogen and progesterone receptors (ERa, ERb, GPER, PRA, PRB, mPR, PGRmC1) by RT-PCR in pathological endometrial tissue and peripheral blood mononuclear cells. GABDH was used as a comparison gene. The data obtained made it possible to determine the significance of mononuclear cell receptivity in the pathogenesis of endometrial proliferative processes.

Endometrial Tissues and Mononuclear Cells Receptivity in Pathogenesis of Endometrial Proliferative Processes

Receptivity of Endometrial Tissue and Peripheral Blood Mononuclear Cells in the Pathogenetic Rationale for the Management of Postmenopause Patients With Endometrial Proliferative Processes

Expression level of ERα, ERβ, GPER, PRA, PRB, mPR, PGRmC1 in endometrial tissue and peripheral blood mononuclear cells in patients with endometrial polyps, endometrial hyperplasia, atypical endometrial hyperplasia, endometrial cancer

Pirogov Russian National Research Medical University

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Dendritic Cell Tumor

Neuroendocrine Tumor

Neuroepithelioma

Central Nervous System Stimulants

Antineoplastic Agents

Molgramostim

Sargramostim

Immunomodulating Agents

Immunologic Factors

DOSE/ROUTE/REGIMEN:

1. Treatment Duration: Doses of MC will be administered subcutaneously weekly for 3 consecutive weeks, then monthly for the next 5 months.
2. Dosage: Each dose of MC contains approximately 10 million cells. Each dose is suspended in 500 mcg GM-CSF prior to administration.
3. Mode of Administration: Subcutaneous (SC) injections.

DOSE/ROUTE/REGIMEN:

1. Treatment Duration: Doses of DC-TC will be administered subcutaneously weekly for 3 consecutive weeks, then monthly for the next 5 months.
2. Dosage: Each dose of DC-TC contains approximately 10-20 million cells. Each dose is suspended in 500 mcg GM-CSF prior to administration.
3. Mode of Administration: Subcutaneous (SC) injections.

Comparison of a cancer treatment containing patient specific irradiated tumor cells mixed with antigen presenting immune cells suspended in an immune system stimulant vs. a cancer treatment containing patient specific immune cells suspended in an immune system stimulant

Autologous Dendritic Cell-Tumor Cell Immunotherapy (DC-TC)

Autologous PBMCs in GM-CSF (MC)

Robert O Dillman, MD

The purpose of this research is to evaluate the safety and effectiveness of tumor cell therapy.

This research study is evaluating if a patient-specific experimental therapy for metastatic melanoma will lengthen survival with minimal harmful effects. It is called an experimental therapy (or "study therapy") because it is not yet approved by the U.S. Food and Drug Administration (FDA). This research study will use the patient's own tumor cells,the patient's own dendritic cells (a type of immune cell), and a granulocyte-macrophage colony stimulating factor (GM-CSF, a type of growth factor). GM-CSF is a natural growth factor that stimulates growth of white blood cells in the body. Since 1991, GM-CSF has been used as a standard treatment to help increase the number of white blood cells after chemotherapy.

The patient's dendritic cells are grown in a test-tube with the patient's tumor cells and the growth factor. The resulting solution is called the study therapy. The intent of the study therapy is to make the dendritic cells more effective at fighting the tumor when they are injected back into the patient.

Learn more about this clinical trial at http://TheIntusStudy.com. Type or copy and paste http://TheIntusStudy.com in your browser window.

Autologous Dendritic Cell-Tumor Cell Immunotherapy for Metastatic Melanoma

Phase III, Randomized, Double-Blind, Multicenter Trial of Autologous Dendritic Cells and Irradiated Autologous Tumor Cells In Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) vs. Autologous Peripheral Blood Mononuclear Cells (PBMCs) In GM-CSF for The Treatment Of Metastatic Melanoma

The time frames are estimated time in months (rounded up to the nearest month) from the start of study. The time estimates for the analyses are based on enrolling approximately 250 patients over a 34.8 months period and having a follow up of approximately 17 months after the last patient is enrolled.

* Adverse Events monitoring to assess safety and tolerability
* History \& physical examination, vital signs, clinical laboratory tests (safety), and other tests as clinically indicated adverse event monitoring to assess safety and toxicity

Lisata Therapeutics, Inc.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

biomarker detection

Shirong Zhang, Ph.D

Shirong Zhang, Dr.

This study aims to dynamically monitor the expression profile status of peripheral blood mononuclear cells (PBMC) and the changes in circulating tumor DNA (ctDNA) levels in patients with stage III locally advanced unresectable non-small-cell lung cancer(NSCLC) after concurrent chemoradiotherapy or sequential chemoradiotherapy, and to explore biomarkers related to the immune microenvironment and the optimal time point for immunotherapy after chemoradiotherapy.

Biomarkers of Stage III Locally Advanced Unresectable Non-small-cell Lung Cancer

Dynamic Biomarkers of Immune Microenvironment for Stage III Locally Advanced Unresectable Non-small-cell Lung Cancer

According to the biomarker detection before and after chemoradiotherapy to identify biomarkers related to the immune microenvironment, including the expression levels of NK cells, T cells, B cells and other immune cells reflected by PBMC, as well as the expression levels of ctDNA

Changes in the expression levels of ctDNA and PBMC immune cells before and after chemoradiotherapy to find the optimal time point for immunotherapy

First People's Hospital of Hangzhou

Prostatic Neoplasms

Fluorides

Up to 6 Male prostate cancer patients with metastatic, castration resistant prostate cancer will be enrolled.

19F Cell Sense-labeled PBMC (3 million cells) will be injected intradermally into the upper thigh of each participant above the inguinal lymph node. MRI will be used to image the administration site.

Up to 6 male or female healthy volunteers will be enrolled.

19F Cell Sense-labeled PBMC (3 million cells) will be injected intradermally into the upper thigh of each participant above the inguinal lymph node. MRI will be used to image the administration site.

Peripheral blood mononuclear cells (PBMC) will be isolated from patient whole blood samples and labeled in a GMP facility with GMP grade 19F Cell Sense imaging agent.

These cells will be re-administered to the patient prior to imaging.

19F Cell Sense-labeled PBMC

Participants will undergo Magnetic Resonance Imaging (MRI) at 1 hour and 24 hours following PBMC administration

Gregory A Dekaban, PhD

Paula J Foster, PhD

Sowmya Vuswanathan, PhD

Joseph Chin, MD

Michael Rieder, MD PhD

Gary Brahm, MD

Doreen Matsui, MD

George Dresser, MD

Cell-based therapies in the form of stem cell-based or immune cell-based therapies are becoming important treatment options that are either approved for clinical use or are showing promise in clinical trials. One of the issues regarding cell-based therapies is that, once the cells are injected into a subject, there is no easy way to track where they go, assess whether adequate numbers of cells arrive at the intended therapeutic target and for how long they persist at a given location. To address this issue non-invasive imaging methods have been developed using magnetic resonance imaging (MRI). When used with an appropriate cell labelling contrast agent, Cellular MRI can track cells non-invasively in vivo. Detection of cells is accomplished with an inert imaging agent containing the MRI sensitive fluorine-19 (19F) nuclei. The objective of this study is to demonstrate that 19F-MRI is safe to use in humans so that it can subsequently be used to track cell-based immunotherapies in future clinical trials. The long term goal is to be able to quantify immune cell migration to secondary lymphoid tissues and potentially to tumors and correlate to therapeutic outcomes.

Background: None of the currently available Good Manufacturing Practices (GMP)-grade MRI cell labelling agents are approved for use in Canada. There is one iron oxide nanoparticle GMP grade preparation that is commercially available but it is not suitable for labelling the immune cell populations the investigators are interested in tracking in vivo. The investigators have, instead, chosen to develop the commercially available, GMP-grade 19F-based perfluorocarbon, known as Cell Sense, for the purpose of tracking immune cell-based vaccine therapies in vivo. This agent has been successful used in a phase I clinical trial in United States and is approved for a second trial current recruiting, under the oversight of the FDA.

The cell tracing agent Cell Sense (CS-1000) is an inert, non-metabolizable tracer. As CS-1000 is taken-up and incorporated into the cell traditional pharmacodynamic and pharmacokinetic analyses in animals and humans are not appropriate, as adsorption and biodistribution will vary with cell type, and therefore have not been done. In vitro studies of toxicity towards various cell types did not yield evidence of adverse effects on various cell functions. Cell Sense also was shown to be non-mutagenic using the Ames and Forward thymidine kinase (TK) assays. Some limited skin irritation was observed when \>2,500 fold more Cell Sense than expected to be maximally injected into humans was injected intradermally into rats.

Examples of MRI cell tracking labels include superparamagnetic iron oxide nanoparticles and 19F-containing compounds such as perfluorocarbons. The advantage of using cellular MRI to track cells is that a non-radioactive tracer is used that is suitable for longitudinal studies. MRI offers 3D imaging with exquisite soft tissue contrast. The additional advantage of using 19F over iron-based agents is that 19F is a positive, easily quantifiable contrast cell labelling agent. Furthermore, there is no 19F-background MRI signal in humans whereas MRI involving iron can be confounded by different imaging artifacts and it is a negative contrast agent that is difficult to accurately quantify. The investigators are particularly interested in whether immune cells arrive in secondary lymphoid organs such as lymph nodes.

Study Design:

Open label, dose escalating, single centre, phase I study that will accrue (a) 6 healthy adults and (b) 6 prostate cancer patients.

Three healthy adults and three prostate cancer patients will be enrolled into the first cohort. Whole blood (150 ml) will be obtained by venipuncture. After processing of the blood to obtain peripheral blood mononuclear cells (PBMC), half of the PBMC will be treated with Cell Sense for 8-24 hours. Given the robustness of our data using 5 donors during dry runs, the investigators do not propose to compare labeled vs unlabeled cells as release criteria. However, the investigators will be collecting this data for information and research purposes. Three million (3 x 106) Cell Sense labeled autologous PBMC will be administered intradermally to the cohort 1 subjects. The three healthy adults and the 3 prostate cancer subjects will be tested concurrently.

If no grade 2 or higher adverse events are observed with the 1st cohort, concurrent enrolment will proceed to recruit a second set of 3 healthy adult subjects and the second set of 3 prostate cancer patients. The second cohort of subjects will be subjected to the same design but with an escalation of the dose to 2-3 x 107 Cell Sense-labeled autologous PBMC administered intradermally.

Endpoints:

Primary Endpoints:

Determine the feasibility of using Cell Sense to detect and monitor the migration of PBMC in humans

Secondary Endpoints:

* Confirm and further optimize the 19F Cell Sense detection and Hydrogen- 1 (1H) anatomical imaging parameters for imaging using the 19F/1H dual coil.
* Determine if Cell Sense-labeled PBMC migration to the draining lymph node can be detected.
* Determine if the lymph nodes in the area of interest imaged change in size on the injected side compared to the contralateral side.
* Quantify the number of Cell Sense-labeled PBMC detected.
* Evaluate safety parameters (toxicity) as defined by:
* adverse events.
* serious adverse events.
* changes in laboratory determination and vital sign parameters as assessed by medical history, physical examination and clinical laboratory tests.

The following categories will be used to grade any adverse events:

* Grade 1: does not interfere with daily activity,
* Grade 2: interferes with daily activity, no treatment required, except paracetamol,
* Grade 3: prevents daily activity or requires treatment.
* Grade 4: Life-threatening

NIH and FDA (or CTCAE v 4.0) guidelines will be used to determine the severity of adverse events

Tracking Peripheral Blood Mononuclear Cells With Fluorine MRI

A Phase I Study Evaluating the Feasibility of Using Fluorine-19 Cell Sense to Image Human Peripheral Blood Mononuclear Cells In Vivo

This process will involve testing if the number of PBMC at the site of injection can be visualized and quantified following injection. Signal produced by labeled cells is linearly related to the number of cells. In vivo quantification has been demonstrated in animal modes, but not in a clinical setting to date.

If necessary, specific imaging parameters will be adjusted to optimize for clinical anatomical and 19F cell tracking imaging.

PBMC are required to migrate to the lymph node for optimum therapeutic effect. Here the investigators will determine if 19F-MRI contains the necessary imaging sensitivity to detect migration.

University of Western Ontario, Canada

Ontario Institute for Cancer Research

Gregory A. Dekaban

Professor

Recurrence

Nivolumab

Atezolizumab

Antibodies

Vaccines

Immune Checkpoint Inhibitors

Ipilimumab

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

In Part 1, SQZ-PBMC-HPV as a monotherapy is administered on Day 1 of every 3 week cycles for up to a year. In Cohort 3 (double-priming), SQZ-PBMC-HPV is also administered on Day 2 of Cycle 1. There are at least 3 groups ("Cohorts") in this Phase as follows:

* Cohort 1: specified dose SQZ-PBMC-HPV
* Cohort 2: specified dose SQZ-PBMC-HPV
* Cohort 3: specified dose SQZ-PBMC-HPV double-priming

In Part 2, SQZ-PBMC-HPV in combination with immune checkpoint inhibitors (1) atezolizumab, (2) ipilimumab, (3) nivolumab, or (4) nivolumab and ipilimumab, is administered every 3 weeks for up to a year except atezolizumab may be given up to 2 years; and ipilimumab will be administered four times (in a timeframe less than a year) if safety allows. There are 4 groups ("Cohorts") in this Phase as follows:

* Cohort 4: SQZ-PBMC-HPV RP2D (Recommended Phase 2 Dose) plus atezolizumab
* Cohort 5: SQZ-PBMC-HPV RP2D plus ipilimumab
* Cohort 6: SQZ-PBMC-HPV RP2D plus nivolumab
* Cohort 7: SQZ-PBMC-HPV RP2D plus nivolumab and ipilimumab

In Part 3, SQZ-PBMC-HPV is administered at the RP2D to patients enrolled in HPV16+ cancer-type specific cohorts. There are 4 groups ("Cohorts") in this Phase as follows:

* Cohort 8: SQZ-PBMC-HPV RP2D in HPV16+ head and neck cancer patients
* Cohort 9: SQZ-PBMC-HPV RP2D in HPV16+ cervical cancer patients
* Cohort 10: SQZ-PBMC-HPV RP2D in HPV16+ anal cancer patients
* Cohort 11: SQZ-PBMC-HPV RP2D in other HPV16+ cancer patients

antigen presenting cell therapy; therapeutic vaccine consisting of peripheral blood mononuclear cells (PBMCs) manufactured with immunogenic epitopes of HPV16

SQZ-PBMC-HPV

programmed cell death ligand 1 (PD-L1) blocking antibody

cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking antibody

programmed cell death 1 (PD-1) blocking antibody

This is a Phase 1 open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-PBMC-HPV as monotherapy and in combination with atezolizumab or other immune checkpoint inhibitors in HLA-A\*02+ patients with recurrent, locally advanced or metastatic human papillomavirus strain 16 positive (HPV16+) solid tumors. The study includes patients with anal, rectal, cervical, head and neck, penile, vulvar, or vaginal cancer.

Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of SQZ-PBMC-HPV as Monotherapy and in Combination With Atezolizumab or Other Immune Checkpoint Inhibitors in HLA-A*02+ Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors

For SQZ-PBMC-HPV as a single agent (Part 1 and Part 3) and in combination with immune checkpoint inhibitors (Part 2)

Proportion of patients with best response of complete response \[CR\] and/or partial response \[PR\] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Evaluation of the BoR defined as CR, PR, Stable Disease \[SD\], Progressive Disease \[PD\] or Not Evaluable \[NE\] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Defined as the time from first dose of study treatment to death by any cause. This will be censored at the last date patient is known to be alive if death is not observed. For SQZ-PBMC-HPV as a single agent (Part 3 only)

Proportion of patients with best response of complete response \[CR\] and/or partial response \[PR\] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Evaluation of the BoR defined as CR, PR, Stable Disease \[SD\], Progressive Disease \[PD\] or Not Evaluable \[NE\] as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Defined as the time from first dose of study treatment to first overall response of PD by RECIST v 1.1 or to death by any cause. This will be censored at the last RECIST v1.1 assessment if PD/death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Defined as the time from overall response of CR or PR to first overall response of PD by RECIST v1.1 or to death by any cause. This is defined only for patients who have a CR or PR and will be censored at the last RECIST v1.1 assessment if PD/Death is not observed. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

Proportion of patients with best response of CR or PR or SD as defined by RECIST v1.1 criteria. For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

For SQZ-PBMC-HPV as a single agent (Part 1) and in combination with immune checkpoint inhibitors (Part 2)

To determine manufacturing feasibility (Part 1 only)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Endometrial Tissues and Mononuclear Cells Receptivity in Pathogenesis of Endometrial Proliferative Processes	NCT06115577	Endometrial Hyp... Endometrial Hyp... Endometrial Can... Peripheral Bloo... Postmenopause Estrogen Recept... Progesterone Re...	endometrial tis...	53 Years - 80 Years	Pirogov Russian National Research Medical University
Autologous Dendritic Cell-Tumor Cell Immunotherapy for Metastatic Melanoma	NCT01875653	Stage IV Melano... Stage III Melan...	Autologous Dend... Autologous PBMC...	18 Years -	Lisata Therapeutics, Inc.
Biomarkers of Stage III Locally Advanced Unresectable Non-small-cell Lung Cancer	NCT04749407	Non-small Cell ...	biomarker detec...	18 Years - 70 Years	First People's Hospital of Hangzhou
Tracking Peripheral Blood Mononuclear Cells With Fluorine MRI	NCT02921373	Adverse Reactio...	19F Cell Sense-... MRI	40 Years - 85 Years	Western University, Canada
Study of SQZ-PBMC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors	NCT04084951	Adult Solid Tum...	SQZ-PBMC-HPV Atezolizumab Ipilimumab Nivolumab	18 Years -	SQZ Biotechnologies

Spots Global Cancer Trial Database for peripheral blood mononuclear cells