cyrilzakka/clinical-trials huggingface dataset:
L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH

The efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Without early intervention, the median survival time is less than 2 months. Currently, HLH-94 or HLH-04 are the standard HLH treatment regimens, which have improved the disease response rate to approximately 70% and increased the 5-year OS rate to 50%. However, approximately, 30% of the patients remain unresponsive to standard therapy, especially if HLH is lymphoma-associated. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosed as lymphoma-Hemophagocytic Lymphohistiocytosis.
* EBV-DNA in peripheral blood \> 1000 copies/ml or EBER detected in tissue specimens.
* Age 18\~65，gender is not limited.
* Estimated survival time ≥ 1 month.
* Cardiac ultrasound LVEF≥50%; No Active bleeding of the internal organs(digestive tract, lung, brain, etc.); If the patient has dyspnea, oxygenation index \>250.
* Signed informed consent.

Exclusion Criteria:

* Heart function above grade II (NYHA).
* Severe myocardial injury：TNT、TNI、CK-MB \> 3 ULN.
* Accumulated dose of doxorubicin above 400mg/m2 、epirubicin above 750mg/m2、pirarubicin above 800mg/m2 or the patients treated with anthracycline induced cardiovascular disease.
* Pregnancy or lactating Women.
* Allergic to pegylated liposomal doxorubicin，etoposide，or PD-1 antibody.
* Thyroid dysfunction.
* HIV antibody positivity.
* Acute or chronic active hepatitis B (HBsAg positivity, HBV DNA negative acceptable), acute or chronic active hepatitis C (HCV antibody negatively acceptable; HCV antibody positivity, HCV RNA negative acceptable).
* Participate in other clinical research at the same time.
* The researchers considered that patients are not suitable for the study.
Maintenance Therapy With Histamine Dihydrochloride and Interleukin-2 in Adult Acute Myeloid Leukemia (AML) Patients With Measurable Minimal Residual Disease (MRD)- a Non-interventional Study (NIS)

This is a non-interventional multi-center study (NIS) in adult patients with AML in first complete remission with measurable minimal residual disease (MRD). Patients are eligible when gene status was already determined for previous induction and consolidation therapy of AML and showed carrier of NPM1, CBFβ-MYH11, or MLL-AF9 mutation. The study objective is to observe the impact of pre-emptive therapy with histamine dihydrochloride (HDC) and interleukin-2 (IL-2) with regard to assess leukemia-free survival/time to relapse and to monitor MRD level trend over time. HDC and IL-2 are approved drugs for AML patients in first complete remission. Therapy is administered for 10 treatment cycles as outlined in the Summary of Product Characteristics.


Eligibility Criteria:
Patient eligibility criteria in accordance to the summary of Product Characteristics:

* Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification (including de novo AML, t-AML and s-AML) in first complete remission (defined as less than 5% blasts in a normocellular bone marrow assessed prior to the treatment start)
* AMLSG BiO participation incl. favourable opinion
* Presence of NPM1 mutation, CBFB-MYH11 or MLL-AF9 fusion genes as assessed in one of the central AMLSG reference laboratories.
* Measurable MRD values (non-negative values after consolidation therapy or increase in values over the threshold during follow-up in complete remission)
* The patient must be informed of the observation and written informed consent regarding data privacy obtained.
* Consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and all other treating physicians about observation participation
* No continuing systemic treatment with clonidine, steroids, and/or H2 receptor blocking agents.
Social-environmental, Psychosocial, Behavioral, Clinical and Biological Drivers of Disparities in Liver Disease Progression Among Korean American With Chronic Hepatitis B Infection

This study explores how psychosocial factors (e.g., chronic stress, depression) may lead to liver disease progression such as liver cirrhosis or liver cancer among Korean American chronic hepatitis B infection patients. Gathering health information over time from Korean Americans with chronic hepatitis B infection may help doctors find better methods of treatment and on-going care.

PRIMARY OBJECTIVES:

I. To estimate the prevalence of chronic hepatitis B (CHB) phenotype and liver disease severity at enrollment visit, and model how multiple social-environmental, psychosocial, behavioral, clinical and biological attributes are associated with variation in CHB phenotype and disease severity.

II. To identify how these same attributes are associated with disease progression over time.

SECONDARY OBJECTIVE:

I. To examine the moderating effects of these multi-level factors on the relationship between liver disease progression and adverse liver disease outcome (e.g., hepatocellular carcinoma \[HCC\]), as well as mediating effects of liver disease progression on the relationship between psychosocial factors and liver cancer or death.

EXPLORATORY OBJECTIVE:

I. Using an explanatory mixed methods approach, to understand the care-seeking behaviors, and dynamics of care, within an ethnically concordant liver disease care model, and how these factors may have both direct and mediational effects on adherence, treatment effectiveness, and adverse disease outcomes.

OUTLINE:

Patients participate in interviews over 20-40 minutes and undergo collection of hair samples at baseline and 18-24 months. Patients' medical records are also reviewed.

Eligibility Criteria:
Inclusion Criteria:

* Provide signed and dated informed consent form
* Willing to comply with all study procedures and be available for the duration of the study
* Korean-American male or female, age over 18 and older
* CHB Patients who have lab and medical record data (including hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\] viral load, hepatitis B virus e Antigen \[HBeAg\] status, and liver enzyme values) exist from 2015 or before

Exclusion Criteria:

* Patients who have received a diagnosis of HCC, although they may have been diagnosed with cirrhosis
* Patients who have been diagnosed with other viral infections (hepatitis C virus \[HCV\], human immunodeficiency virus \[HIV\], etc.)
* Patients who have total baldness
Sirolimus in Graves' Orbitopathy

Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug.

The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO.

The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.

Study Design: observational

Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared.

Study Timeline

Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)

Eligibility Criteria:
Inclusion Criteria:

1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
2. A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
3. Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
4. Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
5. Male and female patients of age: 18-75 years

Exclusion Criteria:

1. Optic neuropathy
2. Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment
3. Mental illness that prevents patients from comprehensive, written informed consent
Stress Sensitivity and Reward Responsivity in Depression

The goal of this project is to learn more about the different ways in which people process information that is stressful and rewarding, and how abnormalities in these two processes are related to depression.

Participants will participate in two 3-hour sessions separated by a week at Providence Care, Mental Health Services, and a third, 1.5-hour session at the Queen's MRI Facility. At the first session participants will complete a packet of questionnaires about their mood and take part in an interview about their mood, medications, drug use, and any other symptoms, as well as an interview about their relationships with their parents and any experiences of abuse. At the second session participants will participate in a stress test, which involves giving a speech to a panel. The investigators will also collect saliva samples to look at stress hormones. Participants will also complete a task on the computer that involves looking at cartoon faces and making decisions about them. At the third session, the investigators take images of of participant's brain using a magnetic resonance scanner.

Participants are invited to participate in a 6-month follow-up for this study, which would involve the same procedure as outline above.

Eligibility Criteria:
For Depressed Participants:

Inclusion Criteria:

* Outpatients aged 18-65
* Currently suffering from unipolar depression
* Fluency in English, sufficient to complete the interviews and self-report questionnaires

Exclusion Criteria:

* Clinical diagnosis of bipolar disorder, psychotic disorders, current alcohol/substance dependence, or significant medical comorbidity
* Treatment-resistant (defined as failing more than 3 trials of anti-depressant medication)
* History of neurological insult (e.g., concussion), neurological disease, seizure disorder
* Smokers
* Pregnant women
* Endocrine disorders
* High suicidal risk, defined by clinician judgement

For Healthy Control Participants:

Inclusion Criteria:

* Adults aged 18-65
* No history of Axis I disorders according to DSM-IV-TR criteria, as determined by the SCID
* No first-degree relatives diagnosed with bipolar disorder
* Fluency in English, sufficient to complete the interviews and self-report questionnaires

Exclusion Criteria:

* History of neurological insult (e.g., concussion), neurological disease, seizure disorder
* Smokers
* Pregnant women
* Endocrine disorders
A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma

This is an open label, multi-center, phase 1 safety run-in and phase 2 study of BBI608 in combination with temozolomide in patients with recurrent or progressive glioblastoma who have not received prior bevacizumab therapy.

In arm A, patients who are candidates for surgical resection will receive BBI608 as monotherapy prior to resection, followed by post-operative BBI608 administered in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, in combination with temozolomide.

In the phase 1/dose-limiting toxicity (DLT) cohort portion of this study, pharmacokinetics will be evaluated for both arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical resection.

Eligibility Criteria:
Major Eligibility Criteria

1. Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements.
2. A histologically confirmed supratentorial glioblastoma (GBM) at first recurrence/progression (except for transformation from previous low grade glioma) following standard front-line therapy, for which treatment with temozolomide (TMZ) would be acceptable as determined by the Investigator
3. Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy.
4. Patients may or may not be candidates for repeat surgical resection of the recurrent/progressed GBM.
5. Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a minimum of 12 weeks following completion of chemoradiation or radiation therapy.
6. Patients must have measurable or non-measurable disease by response assessment in neuro-oncology Response Assessment in Neuro-oncology (RANO) criteria
Study of Safety, Tolerability, and Pharmacokinetics of REGN2477 Alone and in Combination With REGN1033 in Healthy Postmenopausal Women and Healthy Adult Men

The primary objective is to assess the safety and tolerability of REGN2477 alone and combined with REGN1033.

The secondary objectives are to:

* Assess the effect of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on thigh muscle volume
* Assess the effects of REGN2477 alone, REGN1033 alone, and REGN2477 + REGN1033 in combination on total and regional body composition
* Evaluate the Pharmacokinetic (PK) profile of REGN2477 and REGN1033
* Assess immunogenicity of REGN2477 or REGN1033
* Assess REGN2477 or REGN1033 target engagement


Eligibility Criteria:
Key Inclusion Criteria:

* Postmenopausal women age 45 to 70 years and age 35 to 60 years inclusive for men not intending to father children
* BMI between 18 to 32 kg/m2, inclusive
* Willing and able to maintain current diet, supplements and physical activity level throughout the study
* Provides signed informed consent

Key Exclusion Criteria:

* Significant illness or history of significant illness
* Contraindication to MRI
* History of human immunodeficiency virus (HIV); hepatitis B or hepatitis C virus (HCV)
* History of immobilization, major surgical procedure, fracture, or major trauma within 9 months prior to screening
* History of significant gynecological disorders or malignancies; history of breast malignancies (uterine fibroids or dysfunctional uterine bleeding is acceptable)
* Inconsistent vigorous physical activity (on fewer than 5 days per week), such as intermittent weight lifting
* History of hypersensitivity reactions to tetracycline antibiotics (includes doxycycline), vaccines, or biologics
* Use of agents that alter muscle mass that have not been at a stable dose for 3 months prior to screening (includes protein supplements), or use of any weight altering or anabolic steroid drugs (includes drugs for obesity, diuretics, testosterone)
* Participants treated with a biologic therapy or biologic immunotherapy in the previous 12 weeks prior to screening and during the study

Note: Other protocol Inclusion/Exclusion criteria apply.
Effects of Flavanoids in Essential Hypertension, Type 2 Diabetes and Healthy Persons

Flavanols are natural substances who are frequently found in our nutrition. A lot of research has already been executed in the past to investigate what effects this flavanols could have in the human population. Based on these examinations, the investigators think and suggest that flavanols can have positive effects on the vascularly system, more specifically on the peripheral and cerebral blood vessels. The effects are only observed in a healthy populations, meanwhile patient populations like diabetes patients could really benefit from this. This is why the investigators will execute this study.

The study population is divided into 3 main groups, namely healthy controls, patients with diabetes type 2 (defined by American Diabetes Association's (ADA)) and patients with essential hypertension (the latter group is again divided into 3 subgroups: use of betablockers, angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-receptor blockers (ARBs). Each main goup will consist of minimal 20 subjects.

In this interventional study the investigators ask the patient to come twice. One time they get capsules with real flavanols and the other time they get capsules with a placebo. The study will be double blinded so nor the investigators, nor the patients now at which investigation they get the real flavanols or the placebo.

Before and after the intake of these capsules, a few measurements will take place. These measurements will be compared on the one hand with the second investigation day (inter-patients and intra-patient) and on the other hand with the pre-intake measurements (intra-patient).

The different examinations are a Flow-mediated dilatation (FMD) test, blood pressure analysis and an exercise test.

The investigator who performs the FMD-test, followed a course and needed to pass an examination.

The blood pressure measurements will be continuously for 20 minutes to avoid to much bias.

Eligibility Criteria:
Inclusion Criteria:

* men and woman, age 18 - 85 years old, diabetes type 2 and/or using 1 sort of blood pressure lowering medication (betablockers, calcium-antagonists, RAAS-inhibitors)

Exclusion Criteria:

* GENERAL: diabetes type 1, maturity-onset diabetes of youth (MODY), Latent Autoimmune Diabetes of the Adult (LADA), smokers, alcohol abuse, active cancer, chronic inflammatory disease
* MICROVASCULAR: retinopathy, diabetic/hypertensive nephropathy, peripheral sensoric neuropathy, autonomic neuropathy
* MACROVASCULAR: cardiovascular diseases, cerebrovascular diseases, active or chronic palindromic vasculitis
* MEDICATION with impact on endothelial function: NO-containing medication, phosphodiesterase Type 5 -inhibitors
* DISEASES who can affect the exercise test: chronic obstructive pulmonary disease (COPD) with Global Initiative for Chronic Obstructive Lung Disease (GLOD) -stages III and IV, Heart failure class 3 and 4, serious musculoskeletal diseases
* OTHER: pregnancy
Role of T Helper 17 and Regulatory T Cells in Delayed Graft Function

Delayed graft function (DGF) increases risk of acute rejection after kidney transplantation (KTx). Interleukin-6, which is produced in DGF, is critical in directing naive T helper cells differentiation towards T helper 17 (Th17) and away from regulatory T (Treg) cells. The investigators hypothesize there is an increase in Th17 and a decrease in Treg expression in KTx recipients with DGF compared to those without, leading to immunologic consequences. The investigators will test their hypothesis by measuring in both groups expression of Th17, Treg, and related cytokines in blood, urine, kidney biopsy, and kidney preservation fluid, and correlating these results with immunologic events.

All adult recipients of a primary kidney transplant will be eligible. Subjects will have blood samples drawn from which we will isolate lymphocytes and analyze the Treg population based on surface markers as well as a functional assay. The measures of Treg function will be compared to outcomes including DGF, graft survival and graft function, as well as the development of immunological complications such as donor-specific antibody production, acute rejection, IFTA and opportunistic infection.

Eligibility Criteria:
Inclusion Criteria:

* Kidney transplant recipients

Exclusion Criteria:

* None
Amotosalen-Ultraviolet A Pathogen-Inactivated Convalescent Plasma in Addition to Best Supportive Care and Antiviral Therapy on Clinical Deterioration in Adults Presenting With Moderate to Severe COVID-19

This project investigates individual treatments using convalescent severe acute respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma in SARS-CoV-2 infected patients at risk for disease progression. In addition to standard of care, SARS-CoV-2 infected patients for whom blood group compatible convalescent plasma is available and who are willing to sign the informed consent receive convalescent plasma. Only patients with moderate to severe disease at risk for transfer to intensive care unit or patients at the intensive care unit with limited treatment options will be treated.


Eligibility Criteria:
Inclusion Criteria for donors:

* male patients who have been tested positive for SARS-CoV2 at University Hospital Basel, Switzerland or in the near surroundings more than 10 days before enrolment
* 18-60 years of age
* asymptomatic (thus successfully overcome COVID-19) \>14 days back
* two consecutive naso-pharyngeal swabs tested negative for quantitative PCR-test for SARS-CoV-2 prior to plasma donation to demonstrate infection Resolution, or more than 28 days asymptomatic after SARS-CoV2 infection
* Body weight of at least 50 kg
* donor eligibility criteria according to the Swiss Red Cross Blood Transfusion Service as for regular blood donation

Exclusion Criteria for donors:

* Female donors are excluded from plasma donation
* Treatment with Actemra® (Tocilizumab) in the course of COVID-19
* Current hospitalization
* Current or previous relevant medical conditions that pose a risk for the donor

Inclusion Criteria for COVID-19 infected patients:

* SARS-CoV-2 infection confirmed by PCR in respiratory secretions (naso- pharyngeal swab, broncho-alveolar lavage, sputum)
* hospitalized
* pulmonary infiltrates compatible with COVID-19 on CT-scan
* availability of blood group compatible convalescent plasma
* signed informed consent