Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

All Conditions

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Peripheral blood mononuclear cells (PBMC) will be collected from healthy volunteers and patients who present with different diseases that involve or implicate the immune system dysregulation (HIV infection, autoimmune diseases and cancer). These PBMC will be studied in vitro for a number of functional parameters, including generating soluable factors that inhibit HIV infection, developing patterns of immune dysregulation, and inducing apoptotic T cell death. The purpose of such studies is to obtain insight into the mechanisms of natural resistance to viral infections, AIDS pathogenesis, and disease-induced immune dysregulation.

In Vitro Study of Peripheral Blood Mononuclear Cell Function in Healthy Individuals and Patients

National Cancer Institute (NCI)

Neoplasms

Blood and Lymph Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Syndrome

Lymphosarcoma

Patient with Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NEIL)

Analysis of biological sample and clinical data

Eleonora Gambineri

Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterised not only by an infectious diathesis, but by a wide variety of other clinical manifestations. Lymphoma is one of the most common malignancies in children and may be the first clinical manifestation of IEI, thereby 'hiding' the immune defect and delaying genetic/immunological diagnosis. Lymphomas, especially non-Hodgkin's lymphomas (NHL) are frequently associated with congenital defects of the immune system, in particular diffuse large B-cell lymphoma and Burkitt's lymphoma. Preliminary analyses conducted on 6 patients diagnosed with NHL allowed the identification of genetic variants in genes associated with IEI. In clinical practice, the diagnosis and choice of therapeutic treatment in patients with immunodeficiency-associated lymphoma are decisive and, due to the complex pathophysiology of the disease, it is not always possible to identify the boundary between benign and malignant proliferation. The identification of an undiagnosed immunodeficiency in patients with lymphoma will ensure the opportunity to apply targeted therapies, such as allogeneic haematopoietic stem cell transplantation, instead of standard clinical management based mainly on chemotherapy. The study aims to identify possible congenital defects of immunity, i.e. genetic disorders affecting the immune system, as responsible for the development of haematological malignancies. Through a multidisciplinary approach involving immunological analyses, genetic analyses and a thorough examination of clinical manifestations, we aim to characterise the immunological component underlying the development of paediatric lymphomas.

Patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL) aged and patients with previous lymphoma and signs of immunodeficiency

Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas

Characterizing the role of the immune system in the pathogenesis of polyclonal and clonal lymphoproliferation. In particular, the main aim of our study will be the identification, by means of second-generation genetic analysis and functional validation studies of the identified variants, of congenital immune system defects in patients with lymphoid neoplasia

Investigating Cell-Free DNA for specific molecular alterations in lymphomas, in order to monitor the follow-up of patients affected by lymphoma and to identify early onset of clonality in patients with already diagnosed congenital defects of the immune system at risk of developing malignant lymphoproliferation.

Meyer Children's Hospital IRCCS

Principal Investigator

IgA Deficiency

Blood Protein Disorders

Hematologic Diseases

All Drugs and Chemicals

Immunoglobulin A

B-Lymphocyte Stimulator (BLyS)

This study will examine the safety of BlyS, an experimental drug being developed to treat immune deficiency. As of July 17, 2001, 7 persons with common variable immune deficiency (CVID) have received BlyS, with no problems reported. This study will test the safety of the drug in people with IgA deficiency.

Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, electrocardiogram (EKG), chest X-ray and a breathing test (spirometry).

Participants will be divided into five groups of three persons each to receive different doses (0.1, 1, 5, 15 or 45 micrograms/kilogram of body weight) of BlyS. The first group will receive a single dose at the lowest dose level (0.l mg). Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group. The drug will be injected under the skin, with vital signs (temperature, pulse, blood pressure and breathing rate) monitored for one hour after dosing. Blood samples will be collected several times on the day of dosing (before the dose and at 1.5, 3, 5, 8 and 12 hours after the dose) and again at 1,2, 4, 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety. Participants receiving one of the three higher doses will have additional blood samples collected 36, 48 and 60 hours after the dose. Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects. A total of 289 ml (1.2 cups) of blood will be collected.

Blood will be checked for changes in blood count, kidney and liver function, antibody levels and autoimmune problems. Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels.

Urine samples will also be collected during the study.

B Lymphocyte Stimulator (BLyS (Trademark)) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that is expressed on peripheral blood monocytes and dendritic cells. Cellular receptors for BLyS are detected on mature immunoglobulin (Ig) expressing B-lymphocytes. In vitro studies show that BLyS increases B cell number, Ig production, antigen-specific immunoglobulin response, and induces production of secretory IgA.

B-cells collected from patients with Common Variable Immune Deficiency show evidence for BLyS binding to B cells and enhanced immunoglobulin secretion.

In 28-day toxicology studies in mice, pharmacological effects were restricted to B lymphoid tissues including B lymphocyte hyperplasia, increased splenic weight without significant increase in spleen size, and increased immunoglobulin production. Murine models suggest that all of the pharmacological effects are fully and rapidly reversible.

The biological profile of BLyS suggests that it may have therapeutic utility in the treatment of immunodeficiency disorders characterized by low or absent immunoglobulin such as selective IgA deficiency (IGA-D).

Risk that BLyS might contribute to IGA-D complications has been assessed. A series of special in vitro and short-term in vivo studies have shown BLyS does not enhance tumorigenicity or allergy/hypersensitivity. Enhanced autoimmunity with immune complex formation could not be ruled out in two mouse studies in which BLyS was administered at higher doses on multiple dosing schedules. Renal changes with glomerular protein deposits were noted in a subset of mice treated at 0.1 and 1.0 mg/kg in the first study and 0.3 and 3.0 mg/kg in the second study. Renal changes have not been reproducible in either of 2 repeat mouse studies designed to replicate conditions on the first study. Renal changes were not observed in the GLP toxicity study in which mice were treated for 4 weeks with BLyS followed by a 2-week recovery period, or in an exploratory monkey study.

This study is a phase I; single-dose, open-label, non-randomized, dose escalation study of BLyS administered subcutaneously to a total of 20 evaluable subjects with IgA-D. Each subject will receive a single dose of BLyS.

The proposed study consists of a screening phase, a 1-day treatment phase with pharmacokinetic sampling, day 2 and day 3 follow-up, and 1, 2, 4, 8, and 12-week acute safety evaluations. Dose escalation to the next cohort is dependent on results of the 2-week acute safety evaluation. Autoimmunity and interim infection history will be evaluated 4-6 weeks and 6 and 12 months. Long-term data will be collected on incidence of malignancy for a minimum of one year.

B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency

A Phase I Dose Escalation Study of B-Lymphocyte Stimulator (BLyS) Administered Subcutaneously in Patients With Selective IgA Deficiency

Respiratory Tract (Lung and Bronchial) Diseases

COVID-19

Frailty

Anti-Infective Agents

Metronidazole

The study planned to collect demographic information, disease history, COVID-19 symptomatology, COVID-19 molecular test details, COVID-19 serological test results, and biobanking of biological specimens (PBMCs, sera, plasma). In addition, clinical analyses, anamnestic data, and pharmacological treatment pieces of information were collected.

Collecting biological material from frail patients, with or without COVID-19

The COVID-19 pandemic started in December 2019 in Wuhan, the Chinese province of Hubei. Compared to the period of the first epidemic wave (March to May 2020), in the period of the second epidemic wave (October 2020 to July 2021), deceased people have a more significant clinical complexit, as demonstrated by the higher number of comorbidities.The need to allocate significant amounts of healthcare resources to the COVID-19 emergency, deferral of routine healthcare visits, and invitation to avoid medical controls, if not strictly necessary, may have led to interruptions of disease management undersupply of chronic treatments. Consequently, the health status of patients with chronic pathologic conditions have worsened during and beyond the crisis. Patients with cancer, autoimmune disease, and immune deficiencies represented populations with varying immunocompetence, which made translate into higher susceptibility to SARS-CoV-2 and, for this reason, we defined them as frail populations.The main goal of the study was to propel the field of COVID-19 impact on particularly vulnerable categories of patients. The findings of this study could aid in determining the conditions under which healthcare organizations must operate in the event of a pandemic in order to protect patient's rights to care.

Approaches and Metrics in Fraily Patients During COVID-19 Era

Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19.

Presence or not of SARS-COV2 infection Presence of specific tumor or HIV-1 infection or psoriasis

Regina Elena Cancer Institute

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Anemia, Sickle Cell

Thalassemia

Hematologic Neoplasms

Anemia

Hemoglobinopathies

Metabolism, Inborn Errors

Fanconi Syndrome

Fanconi Anemia

Hemolysis

Anemia, Hemolytic

Anemia, Hemolytic, Congenital

Genetic Diseases, Inborn

Anemia, Hypoplastic, Congenital

Anemia, Aplastic

Bone Marrow Failure Disorders

Pancytopenia

Congenital Bone Marrow Failure Syndromes

Bone Marrow Diseases

DNA Repair-Deficiency Disorders

Metabolic Diseases

Sickle Cell Anemia

Congenital Aplastic Anemia

Antineoplastic Agents

Thiotepa

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital

Janel Long-Boyle, PharmD, PhD

Thiotepa is a chemotherapy drug used extensively in bone marrow transplantation. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, triethylene phosphoramide (TEPA). The goal of this study is to determine what causes some children to have different drug concentrations of thiotepa and TEPA in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that certain clinical and genetic factors cause changes in thiotepa and TEPA drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.

Thiotepa is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric hematopoietic cell transplantation (HCT) to promote stem cell engraftment. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, TEPA.

This is a single-center, prospective, non-interventional pharmacokinetics (PK) study investigating the clinical pharmacology of thiotepa and TEPA in 60 children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital. Patients would receive thiotepa regardless of whether or not they decide to consent to PK sampling.

Thiotepa doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing thiotepa and TEPA exposure in pediatric HCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow the investigators to investigate drug levels in a pediatric population that would otherwise not be feasible using traditional intensive PK sampling.

Subjects will undergo PK sampling of plasma thiotepa and TEPA drug concentrations over the duration of thiotepa therapy (3 to 5 days).

To evaluate sources of variability impacting thiotepa and TEPA exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.

A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients.

To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant.

Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients

Population Pharmacokinetics and Pharmacodynamics of Thiotepa and TEPA in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (HCT).

Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance

Death due to any cause within 1 month post-transplant will be considered an event.

Death due to any cause within day 3 months post-transplant will be considered an event.

Death due to any cause within day 1 year post-transplant will be considered an event.

University of California, San Francisco

Nervous System Diseases

Gland and Hormone Related Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Adrenoleukodystrophy

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Aplastic Anemia

Acute Graft Versus Host Disease

X-linked Adrenoleukodystrophy

Adrenomyeloneuropathy

The CliniMACS CD34 Reagent System is a medical device that is used in vitro to select and enrich CD34+ cells from heterogeneous hematologic cell populations for transplantation in cases where this is clinically indicated.

CliniMACS CD34 Reagent System

Erin Arbuckle

Joanne Kurtzberg, MD

The objective of this study is to make T-cell depleted stem cells from a family member who is a half match (haplo-identical) available on an expanded access basis to patients receiving one or two unrelated cord blood transplants who are at a higher risk of not engrafting in a safe amount of time. The purpose of the related stem cells is the give the bone marrow a "jump start" towards recovery. Ultimately, the cord blood cells will grow and permanently rescue the bone marrow.

The primary purpose of the study is to provide expanded access of T-cell depleted haplo-identical stem cells for patients receiving allogeneic transplantation from a related haplo-identical donor and an unrelated, umbilical cord blood (UUCB) unit(s) for the treatment of high risk malignancies and non-malignant disorders. The T-cell depleted haplo-identical stems cells are intended to facilitate early, short-term myeloid engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the UUCB cells engraft as the durable and permanent graft. Patients with high risk or refractory malignancies, or non-malignant disorders amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this protocol.

Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants

A Compassionate Release Protocol: Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Allogeneic Transplantation Using a Related Haplo-Identical Donor and Unrelated, Umbilical Cord Blood Donor(s) for the Treatment of High Risk Malignancies or Non-Malignant Disorders Requiring Allogeneic Transplantation

Duke University

Miltenyi Biotec, Inc.

Antibodies

Vaccines

Immunoglobulins

Antibody titers lower than protection level

Antibody titers higher than protection level

Patients with higher antibody titers will accept vaccination. There are two vaccines provided in this study:

hepatitis B vaccine measles-rubella combined vaccine

Vaccination

Patients with higher antibody titers will NOT accept vaccination. But we will keep monitoring their antibody titers.

No Vaccination

Yi-Jin Gao, MD

Xing-Wei Wang, MD

The purpose of this study is to study on compliance, safety and effectivity of vaccination for children with hematologic malignancies or solid tumors and their parents.

Children with hematologic malignancies or solid tumors are all facing with immune deficiency due to the disease, the chemotherapy, the hematopoietic stem cell transplantation or the splenectomy, which greatly increases their chance to get infectious diseases. In this study, we will assess the compliance of children with hematologic malignancies or solid tumors and their parents to accept vaccination after finishing treatments, follow up with untoward effect questionnaires to assess the safety, obtain the serum of children patients to test antibody titers and assess the effectivity, provide clues for the study of vaccination in children with hematologic malignancies or solid tumors and provide a scientific basis for the formulation and reunification of vaccination programs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
In Vitro Study of Peripheral Blood Mononuclear Cell Function in Healthy Individuals and Patients	NCT00342485	Cell Function		18 Years -	National Institutes of Health Clinical Center (CC)
Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas	NCT06332196	Immune Deficien...	Analysis of bio...	1 Day - 24 Years	Meyer Children's Hospital IRCCS
B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency	NCT00024934	IgA Deficiency	B-Lymphocyte St...	-	National Institutes of Health Clinical Center (CC)
Approaches and Metrics in Fraily Patients During COVID-19 Era	NCT05792891	Frailty Oncology Immune Deficien...	Collecting biol...	18 Years -	Regina Elena Cancer Institute
Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients	NCT03609840	Hematologic Mal... Nonmalignant Di... Immune Deficien... Hemoglobinopath... Genetic Inborn ... Fanconi Anemia Thalassemia Sickle Cell Dis...	Thiotepa	- 17 Years	University of California, San Francisco
Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients	NCT03609840	Hematologic Mal... Nonmalignant Di... Immune Deficien... Hemoglobinopath... Genetic Inborn ... Fanconi Anemia Thalassemia Sickle Cell Dis...	Thiotepa	- 17 Years	University of California, San Francisco
Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants	NCT01881334	Hematologic Mal... Inborn Errors o... Immune Deficien...	CliniMACS CD34 ...	- 65 Years	Duke University
Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas	NCT06332196	Immune Deficien...	Analysis of bio...	1 Day - 24 Years	Meyer Children's Hospital IRCCS
Vaccination for Children of H&O and Their Parents	NCT03373656	Vaccination Hematologic Mal... Solid Tumor, Ch...	Vaccination No Vaccination	- 18 Years	Children's Cancer Group, China

Spots Global Cancer Trial Database for immune deficiency