cyrilzakka/clinical-trials huggingface dataset:
Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion

Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. In humans, we previously reported the positive results of a first clinical trial using Treg depletion for anti-tumor response amplification in the field of allogeneic hematopoietic stem cell transplantation (HSCT). The present project aims at developing this anti-tumor immunotherapeutic strategy in the same setting, i.e. donor lymphocyte infusion (DLI) for relapsing hematological malignancies after HSCT, using a new selection marker: CD127. The choice of this new strategy is supported by our results of a retrospective clinical study and pre-clinical data. Using human cells, this studies demonstrated, in vitro and in vivo in animal murine models, that Treg depletion through CD127 positive selection is much more efficient to improve allogeneic immune responses of donor T-cells as compared to the previous strategy using the CD25 marker.


Eligibility Criteria:
Inclusion Criteria:

* Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
* Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
* Haematological relapse (molecular, cytogenetic or cytological) after HSCT
* Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
* Availability of cryopreserved lymphapheresis
* No loss of chance by using of DLI rather than more incisive anti-tumor agents according to investigator appreciation
* Written informed consent before any intervention necessary for the trial
* Affiliation to a social security regime
* Negative pregnancy test for women of childbearing age participating in the study
* Effective contraceptive methods for men / women in line with the current CTFG recommendations version 1.1

Exclusion Criteria:

* Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
* Patient receiving immunosuppressive treatment for GVHD or any other reason
* Creatinine clearance\< 50 ml/min
* Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 5.0 x upper limit of normal (ULN)
* Serum total bilirubin \> 50µM (expect for unconjugated hyperbilirubinemia due to Gilbert's disease)
* Performance status ECOG\>1
* Severe infection according to CTCAE grading (grade\>2)
* Pregnant or lactating women
* Patient under tutorship, curatorship or legal protection
* Ongoing participation in another interventional research protocol within the same field of immune modulation (through cell therapy or not)
* State medical aid
Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies

Based on a clinical multi-center study of the natural course of inherited retinal dystrophies in Chinese population, screening fundus imaging indicators for patients with Chinese inherited retinal dystrophies, describing the clinical features of Chinese patients with inherited retinal dystrophies, and establishing a diagnosis of hereditary retinal diseases - Follow-up norms; establish a network-based multi-center diagnosis and follow-up platform; obtain a biological sample library of hereditary retinal diseases mainly in China. The research will further improve and enrich the genotype, phenotypic characteristics and natural course of Chinese inherited retinal dystrophies, in order to promote the clinical evaluation of clinical inherited retinal dystrophies and the standardization of genetic diagnosis. It is also the evidence for the best timing for future gene therapy, to obtain the best therapeutic effect, and to provide a theoretical basis for achieving precise treatment.


Eligibility Criteria:
Inclusion Criteria:

1. Patients with IRDs whose mutations have been identified
2. 4\~70 years old
3. Complete 4 basic examinations of the eye: Corrective vision; fundus photography; OCT; ERG

Exclusion Criteria:

1. Has participated in other interventional treatment studies;
2. Patients with severe systemic diseases, mental dysplasia, mental illness;
3. Unable to accept eye examination patients;
4. Traumatic retinopathy, retinal inflammatory disease, paraneoplastic retinopathy, drug toxicity, and rare diseases such as diffuse unilateral subacute optic retinitis
5. At the initial visit, the patient's binocular vision is displayed as no light.
6. Both eyes have a history of internal eye surgery
A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (p) T3-4 cN0M0 Melanoma

Currently, there is no widely used adjuvant treatment available to improve survival after surgical excision of a primary melanoma. In a previous study, loco-regional and systemic immune stimulations, as well as favourable clinical outcomes in terms of sentinel lymph node (SLN) tumor status and recurrence-free survival (RFS) in patients with clinical stage I-II melanoma who received a low dose of toll-like receptor 9 (TLR-9) CPG7909 (CpG-B ODN) intradermally at the excision site of the primary tumor prior to SLN biopsy (SNB) were described. In this phase II trial the investigators had investigated the clinical activity of a next-generation CpG-ODN, IMO-2125, and it's ability to induce loco-regional and systemic immune stimulation in pT3-4 cN0M0 melanoma patients who are scheduled to undergo a combined re-excision and SNB is


Eligibility Criteria:
Inclusion Criteria:

* 18 years or older
* Histologically confirmed primary malignant melanoma cutis with a Breslow tumor depth \>2.0 mm
* Scheduled to undergo a combines re-excision and sentinel node biopsy (SNB)
* World Health Organization (WHO) Performance Status ≤1
* Agreement to use effective contraceptive methods from screening until at least 90 days after the IMO-2125 administration
* Written informed consent

Exclusion Criteria:

* Known hypersensitivity to any oligodeoxynucleotide
* Active auto-immune disease requiring disease-modifying therapy at the tumr of screening
* Pathologically confirmed loco-regional or distant metastasis
* Non-skin melanoma
* Patients with another primary malignancy (some exceptions)
* Active systemic infections requiring antibiotics
* Women who are pregnant or breast-feeding
Evaluation of a Non-invasive Brain Compliance Measurement Device

This is a research study to understand how diabetic ketoacidosis may affect the brain and learning and to see if these changes are transient or permanent. The investigators hope to learn more about how diabetic ketoacidosis may cause changes in brain compliance (by wearing a non-invasive head band/helmet like device from Jan Medical: The Nautilus Neurowave System™ (NNS), learning, talking, behavior, or development. The investigators will compare those results from those with diabetes mellitus to those age and gendered matched healthy controls. Possible subjects in this study have diabetes mellitus and are between the ages of 10 to less than 17 years old OR do NOT have diabetes and are between the ages of 10 to less than 17 years old.

At enrollment, 1 week, 1 month, 3 month, 12 month Computerized neurocognitive testing Wear NNS

MRI of the brain at 3 month and 12 months

Formal neurocognitive testing at 3 months and 12 months

Eligibility Criteria:
Inclusion Criteria:

To be eligible for the study, all subjects must meet the following criteria:

1. Healthy control OR
2. Clinical new onset or established diagnosis of diabetes with diabetes ketoacidosis as defined by the Pediatric Endocrine Society Consensus Statement guidelines
3. Age 10 years to less than 17 years
4. Parent/guardian understand the study protocol and agrees to comply with it.
5. Primary care giver (i.e parent/guardian) comprehends written English. This is due to the fact that questionnaires and neurocognitive testing tools used as outcome measures do not have validated versions in Spanish or other language. Subject comprehends and speaks English.

Exclusion Criteria:

Subjects who meet any of the following criteria are not eligible for the study:

1. History of head trauma with any loss of consciousness
2. History of premature birth (less than 30 weeks of gestation)
3. History of significant developmental delay (lack of single word speech or ability to walk independently by 18 months of age
4. History of neurologic disease independent of diabetes (seizure disorder)
A Safety and Tolerability Study of SCH 721015 in Patients With Transitional Cell Carcinoma of the Bladder (Study P03816)

The purpose of this first-in-human study is to determine the safety and tolerability of SCH 721015 in subjects with transitional cell carcinoma of the bladder.

A nonrandomized, open-label, rising-dose, parallel-group, multi-center study of SCH 721015 in patients with papillary bladder cancer, or carcinoma in situ that is refractory to Bacillus Calmette-Guerin. Subjects will receive a single intravesical administration of SCH 721015 with SCH 209702 in a total volume of 75 mL with a 1-hour dwell time. Subjects who at 3 months post administration demonstrate a complete response (CR on cystoscopy/biopsy and cytology) and who did not experience dose-limiting toxicity will be allowed to receive a second intravesical administration at the same dose level.

Eligibility Criteria:
Inclusion Criteria:

* Histologically proven recurrent transitional cell carcinoma of the bladder, Stage Tis, Ta.
* Patients with recurrent T1 disease who do not wish to have cystectomy.
* Subjects must have failed at least two prior courses of BCG with or without recombinant interferon alpha administration.
* At least 3 months must have passed since last intravesical treatment for bladder carcinoma.
* Subjects must be 18 years of age or older.
* Life expectancy of at least 3 months.
* Adequate performance status (Karnofsky score \>=70%).
* Adequate laboratory values.

Exclusion Criteria:

* Suspected hypersensitivity to interferon alpha.
* Subjects with organ transplants.
* Any known preexisting medical condition that could interfere with the subject's participation in and completion of the study such as:

  * History of psychosis or presence of poorly controlled depression;
  * CNS trauma or active seizure disorders requiring medication;
  * Significant cardiovascular dysfunction within the past 6 months including symptomatic cardiac ischemia, arrhythmia or congestive heart failure requiring hospitalization or emergency room visit within last 3 months;
  * Poorly controlled diabetes mellitus (HbA1C \>10.0%);
  * Unstable chronic pulmonary disease requiring hospitalization or emergency room visit within the last 3 months;
  * Immunologically mediated disease (eg, rheumatoid arthritis, autoimmune hepatitis, immune mediated glomerulonephritis).
* History of any clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administration.
* Untreated bladder infection.
* Positive for hepatitis BsAg or HIV Ab or hepatitis C.
* Immunosuppressive therapy within the last 3 months.
* BCG therapy or intravesical therapy within 3 months.
* Traumatic catheterization within 1 month.
Hyponatremia in the Elderly: Benefit From a Change in Drug Therapy?

Mild hyponatremia is the commonest electrolyte imbalance in the older population. Recently, association between hyponatremia and bone fractures in the ambulatory elderly has been shown.

Mild chronic hyponatremia is causing falls and lead to hospitalisation because of attention deficit.

Symptoms related to hyponatremia can be very subtle and difficult to detect clinically. Twenty elderly patients, retirement homes residents, with serum sodium \< 135mEq/L will be included. They will be randomised. The physician will review the drug treatment of ten patients in coordination with the opinion of pharmacologists. Drug treatment for ten other patients wil remained unchanged during the three months of inclusion.

Useful elements of the medical records of patients randomized to the experimental arm will be forwarded to the Pharmacovigilance Regional Center for opinion pharmacologist. The notice, subject to the attention of physician of retirement homes, give rise to a therapeutic approach towards the patient. It will be followed by weekly monitoring of serum sodium for 4 weeks to evaluate the impact of the intervention. Thus, the effectiveness of medical intervention will be evaluated by an objective biological criteria: serum sodium in the fourth week. Secondary endpoints will evaluate the duration of normalization of serum sodium and check the interest of correcting hyponatremia to improve postural capacities and eventually reduce the number of falls in the medium term (three months).


Eligibility Criteria:
Inclusion Criteria:

* Patient over 65 years Resident of dependent elderly
* Plasma sodium \<135 mmol / l less than a week, confirming earlier hyponatremia within a week to three month agreement given after patient information

Exclusion Criteria:

* Venous system does not allow sampling - Patient not taking medication-Dementia
Closed Loop Ventilation With High Tidal Volumes and Safe Transpulmonary Pressure in COPD (COPD-SAFE)

This study evaluates the safety and efficacy of high tidal volumes generated by "Adapted Support Ventilation (ASV) mode' in mechanically ventilated severe COPD patients. Every patient will be ventilated consecutively with ASV and Volume Control (VC) modes at 2 different levels of minute volume in 2 sets. ASV mode is expected to be safe measured by adequate inspiratory transpulmonary pressures and expected to be as effective as VC mode with lower intrinsic positive end expiratory pressure (iPEEP) levels.

Acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) may require mechanical ventilation. Various mechanical ventilation strategies and modes can be used to manage respiratory insufficiency in such patients. High tidal volumes required for mechanical ventilation of patients with obstructive pathologies is a well-known fact. Adapted Support Ventilation (ASV) is an intelligent closed-loop mechanical ventilation mode which automatically adjusts ventilation to lung mechanics. Led by measured lung mechanics, ASV mode often generates higher than usual tidal volumes during mechanical ventilation of COPD patients, particularly if the minute volume (MV) target is high. Thus, the effects of high tidal volumes on inspiratory transpulmonary pressure (Ptp), and whether Ptp stays within safe limits during ASV mode is of great interest.

Patients with acute exacerbation of COPD who required mechanical ventilation will be enrolled in the first 24 hours of admission to the intensive care unit. All patients will be deeply sedated. An esophageal balloon catheter will be inserted in order to measure transpulmonary pressure. 100 % minute volume target will be calculated in advance as 100 ml per ideal body weight.

Patients will be ventilated with two different MV targets in two sets. 'Adapted support ventilation' and 'volume control (VC)' modes will be used consecutively within each set. While the target minute volume will be 100 % in the first set, the volume target in the second set will be tuned to decrease patients PaCO2 below 45 mmHg. The sequence of ventilation mode will be randomized within each set. Ventilation periods will be 30 minutes with 15 minutes washout period in between. İf Ptp increase above 20 cmH20 at any ventilation mode, the tidal volume will be decreased.

ASV mode is expected to be safe, assessed by adequate inspiratory transpulmonary pressures, and expected to be as effective as VC mode with lower intrinsic positive end expiratory pressure (iPEEP) levels.

Eligibility Criteria:
Inclusion Criteria:

* Acute exacerbation of Chronic Obstructive Lung Disease
* Being intubated for less than 24 hours
* Not being planned to be extubated in 24 hours
* Expiratory time constant (RCexp) more than \> 2.0 s

Exclusion Criteria:

* Restrictive lung pathologies
* Impaired hemodynamic status
* Esophageal pathologies
* Bronchopleural fistula
A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 \[PLX3603\] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Eligibility Criteria:
Inclusion Criteria:

* Advanced solid tumor
* Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Adequate liver, renal and bone marrow function

Exclusion Criteria:

* Participants for whom standard therapy exists and is considered appropriate by the investigator
* Prior treatment with an inhibitor of BRAF (sorafenib allowed)
* Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
* Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
* Anticipated or ongoing anti-cancer therapies other than those administered in this study
* Serious cardiovascular illness within the 6 months prior to study drug administration
Non-interventional Study to Assess the Effectiveness and Safety of Ribociclib in the Adjuvant Therapy of Hormone Receptor Positive (HR+) HER2-negative Stage II and III Breast Cancer in Real Clinical Practice in Russia

This prospective, observational, multicenter study aims at evaluating the efficacy of adjuvant ribociclib in combination with hormone therapy (aromatase inhibitor ± GnRH aginost) in various subgroups of patients with HR+HER2- stage II-III breast cancer in real clinical practice in Russia. Subgroup division will be based on the tumor grade, lymph node involvement, and the response to test hormone therapy. The study will consist of two cohorts: a prospective one with patients receiving adjuvant therapy with ribociclib combined with Aromatase inhibitors (AI), and a retrospective one with patients receiving adjuvant therapy with AI alone. Thus, both primary data collection and secondary use of data will be organized.


Eligibility Criteria:
Inclusion Criteria:

Patients from the prospective cohort of the study must meet all of the following criteria:

1. Signed and dated Informed Consent Form (ICF) not later than 28 days after the initiation of adjuvant therapy with ribociclib in combination with aromatase inhibitors (±GnRH agonists).
2. Age ≥18 years at the time of signing the ICF.
3. Histologically verified HR+ HER2-negative stage II-III breast cancer, for which radical treatment was carried out.
4. The adjuvant hormone therapy with aromatase inhibitors (±GnRH agonists) may be started not earlier than 12 months before initiation of therapy with ribociclib.
5. ECOG performance status 0-1

Patients from the retrospective cohort of the study must meet all of the following criteria:

1. Age ≥18 years at the initiation of hormone therapy.
2. Histologically verified HR+ HER2-negative stage II-III breast cancer, for which radical treatment was carried out.
3. Initiation of adjuvant hormone monotherapy with aromatase inhibitors (±GnRH agonists) in the index period from July 1, 2019 to July 1, 2020.
4. Presence of the necessary information in the source documentation.

Exclusion Criteria:

Patients enrolled in the study in prospective cohort should not meet any of the following criteria.

1. History of therapy with abemaciclib or palbociclib
2. Therapy with ribociclib in combination with AI for more than 28 days at the time of signing the Informed Consent Form
3. Active therapy for other malignant neoplasms
4. Participation in interventional clinical studies at the time of signing the Informed Consent Form

Patients enrolled in the study in retrospective cohort should not meet any of the following criteria.

1. Neoadjuvant or adjuvant therapy with CDK4/6 inhibitors
2. A history of another concomitant malignant neoplasm requiring active therapy
3. Participation in interventional clinical studies at the time of treatment for breast cancer
4. Patients experiencing a recurrence during adjuvant hormone therapy can participate if they meet the other inclusion and exclusion criteria.
Electromyographic Evaluation of Quadriceps During Eccentric Decline Squat

Previous studies have generally investigated patellar tendon stiffness, cross-sectional area of patellar tendon, patellar tendon length, patellar force and patellafemoral forces during decline squat. However, there is just a few study about electromyographic (EMG) activity during the eccentric squating, which is about rectus femoris (RF) recruitment. In the present study the investigators primarly aimed to quantify the activation of RF, vastus lateralis (VL), and vastus medialis obliqus (VMO) during eccentric squat on different decline angle (0, 5°, 10°, 15°, 20°). An additional purpose of our study was to compare the changes in muscle activation at various arc of knee flexion motion (degrees of 0-30, 30-60, 60-90, 0-60, 30-90, 0-90).The investigators hypothesised that the recruitment of RF, VL, and VMO during eccentric squat would differ according to decline angle and arc of motion.

The squat procedure in each condition will be repeated 10 times on a treadmill. The treadmill will be used to adjust the degree of decline in a standard manner. There will be a metronome to keep the speed of exercise in the same rhythm. All squats will be performed with a weighted barbell. The weight of it will be set as in ratio 30% of the participant's body weight

Eligibility Criteria:
Inclusion Criteria:

* had exercised regularly (\>3 days in a week) for at least six months.
* older than 18 years old.

Exclusion Criteria:

* had patellofemoral pain, knee pain otherwise unrelated to the knee extensor mechanism and other injuries that would restrict performance of the tasks (e.g. ankle pathology).