Primary Immunodeficiency

This study evaluates whether a mobile phone-based mHealth Behavioural Change Communication BCC educational intervention can improve the adoption and exclusive use of Liquid Petroleum Gas LPG for cooking among households in semi-rural Bangladesh. Household air pollutants HAP from biomass fuels such as wood, agricultural residue, and cow dung expose almost 3 billion people worldwide, including 89% of people in Bangladesh. In the earlier GEOHealth study, 24 months of LPG use reduced personal PM2.5 exposure by about 58.2% and produced changes in innate immune and inflammatory responses, while chronic cardio-pulmonary markers remained relatively stable. More than 70% of households continued using LPG after the earlier study, although not exclusively. The investigators will conduct a large household-level randomized controlled trial using an mHealth-based educational intervention and will continue following the cohort. The study will examine the long-term effects of HAP reduction on subclinical measures of cardiovascular and pulmonary dysfunction, innate and inflammatory immune function, and antibody response to vaccines. Personal 24-hour and area-wise 5-day exposure to PM2.5 and black carbon will be repeatedly assessed before and after the intervention. Lung function and lung pathology will be assessed using spirometry, Chest X-ray, and high-resolution computed tomography of the chest. Cardiovascular measures will include blood pressure and EKG, while metabolic dysfunction will be assessed using HbA1c and fasting lipid profile. Immune function will be evaluated through immune cell phenotyping, functional cytotoxic killer cells, and oxidative stress of lymphocytes.

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 01 study involving participants with advanced solid tumors that express PD-L1. The study aims to assess the safety, tolerability, biodistribution, radiation dosimetry, and preliminary anti-tumor effects of this treatment. The main goal is to find the maximum tolerated dose and recommended doses for future studies in participants with cancers such as NSCLC, SCLC, triple-negative breast cancer, melanoma, head and neck cancer, endometrial cancer, and others with specific genetic markers. The study includes a pre-screening period for PD-L1 testing if needed, followed by a screening period lasting up to four weeks. Participants undergo a Phase 0 Imaging Period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and dosimetry over two weeks. This may be followed by a Phase 1 Treatment Period with escalating doses of 177Lu-RAD204 administered in cycles lasting six weeks each. Participants may receive multiple treatment cycles based on clinical benefit and safety evaluations. Dose-limiting toxicity is monitored for six weeks after the first treatment dose, and dosing intervals may be adjusted as agreed by the study team. During the study, participants will have imaging scans, safety evaluations, and laboratory tests to track the distribution and effects of 177Lu-RAD204. Researchers will measure pharmacokinetics, radiation dosimetry, and tumor responses up to 30 weeks. Safety and tolerability are closely monitored throughout. Participants must meet specific health and tumor criteria to join and will be observed for any adverse reactions. The total duration of participation varies depending on treatment response and tolerability.

Researchers are evaluating the safety of Immune Globulin Subcutaneous Human, 20% Solution in people with primary immunodeficiency disease PID using a retrospective medical database in Japan called PIDJ2. This observational study collects information about patients who have received this treatment as part of routine care to better understand potential adverse events. The study is sponsored by Takeda and uses existing patient registry data to assess safety outcomes. Participants included in this study are those with PID who have received Immune Globulin Subcutaneous Human 20% infusion following the official package instructions. The study does not administer treatments but analyzes data from the PIDJ2 database collected between January 24, 2024, and January 23, 2029. It focuses on patients whose records include details about use of the study drug and documented adverse events. During the study, researchers will review the database to identify any participants who experienced specific adverse events such as anaphylactic reactions, thromboembolism, or aseptic meningitis up to five years from the initial registration or first dose. The study involves no direct visits or interventions, as it is based on reviewing existing records. The total study period extends until March 31, 2030, allowing long-term safety observations.

Researchers are studying the use of unlicensed cryopreserved cord blood units CBUs for transplantation in both children and adults with blood cancers and other related disorders. This observational study involves patients with hematologic malignancies and various inherited and acquired disorders affecting the blood and immune system. The main goal is to monitor how well neutrophil recovery occurs after transplantation using these unlicensed CBUs in multiple institutions. Participants receive unlicensed cryopreserved CBUs as part of their transplant treatment. The study includes patients of any age receiving these CBUs for approved indications. The protocol focuses on the access and distribution of these unlicensed units rather than a specific treatment intervention. The study gathers data from recipients who receive these CBUs, tracking outcomes after transplantation. Participants are monitored for neutrophil recovery at 60 and 100 days after transplant, defined by a neutrophil count of at least 500mm3. Researchers also collect information on infection transmission, infusion reactions, survival rates at one year, and incidence of acute and chronic graft versus host disease. Platelet recovery is also evaluated. Safety and efficacy outcomes are followed over time to better understand the effects of unlicensed CBUs in this patient population.

Researchers are studying pyrimidine and purine metabolism disorders DPPMs, which affect how the body processes certain chemicals and can lead to problems in the brain, blood, kidneys, and immune system. These disorders vary widely in severity, and this study aims to better understand their causes, features, and outcomes by observing affected individuals, their family members, and healthy volunteers. Participants with DPPMs will visit the clinic at least once a year, sometimes more often. They will undergo physical exams and provide samples of blood, urine, saliva, and stool. Additional tests may include skin and mouth swabs, heart, kidney, brain, and nerve function tests, questionnaires about diet, dental, hearing, and vision exams, learning ability assessments, physical activity monitoring, imaging scans, and photographs. These evaluations may take place over several days, and affected participants can stay in the study indefinitely if they choose. Family members and healthy volunteers will have a single study visit with physical exams and sample collection. Participants will be closely monitored through various medical, laboratory, and imaging studies to gather detailed information. Researchers will analyze genetic material, biochemical markers, enzyme activities, microbiome samples, and clinical data to identify factors related to DPPMs. The study aims to describe features of these disorders and discover genetic, clinical, laboratory, and dietary elements that influence health outcomes. The study may continue for many years, allowing ongoing observation and data collection.

Researchers are studying whether allogeneic hematopoietic stem cell transplantation HSCT can be successfully performed in adults aged 18 to 75 with VEXAS Syndrome, a condition involving severe inflammatory and blood-related problems that are often resistant to standard treatments. This disease causes systemic inflammation and bone marrow failure, leading to serious health issues and increased mortality. The study aims to see if HSCT can reverse the disease symptoms and achieve sustained donor cell engraftment. Participants receive different reduced intensity conditioning regimens depending on their donor match status before undergoing HSCT. Those with an 88 HLA matched donor receive fludarabine and busulfan, while those with a 78 matched or haploidentical donor receive fludarabine, cyclophosphamide, total body irradiation, and busulfan. After transplant, all participants receive drugs to prevent graft-versus-host disease GVHD, including cyclophosphamide, mycophenolate mofetil, and tacrolimus. These treatments are given according to a detailed schedule around the transplant day. Participants undergo extensive screening including physical exams, blood and urine tests, imaging scans, and specialist evaluations. After transplant, they stay in or near the hospital for at least 100 days with weekly visits, followed by study visits at 30, 60, 100, 180, 210, 240, 300, and 360 days post-transplant, then yearly visits for two years and annual phone contacts thereafter. Researchers monitor disease reversal, donor cell engraftment, safety, GVHD incidence, survival, and other outcomes over several years.

Idiopathic CD4 lymphopenia ICL is a condition marked by low levels of CD4 T cells, which makes individuals vulnerable to severe infections, autoimmune diseases, and cancers. This trial evaluates a drug called NT-17 also known as efineptakin alfa or NT-I7 in adults aged 18 to 75 with ICL to assess its potential to increase CD4 T cell counts and study its safety. The trial is an open-label, single-arm, dose-escalation study conducted by the National Institute of Allergy and Infectious Diseases NIAID. Participants must also be enrolled in another NIH protocol related to ICL. Participants will receive three intramuscular doses of NT-17 spaced about 12 weeks apart, with dose levels based on body weight. The drug is administered in the upper arm, thigh, or buttock. Alongside dosing, participants undergo leukapheresis three times, where white blood cells are separated from their blood. Some visits may include rectal swabs, skin exams, biopsies, and imaging. Blood samples are collected before and after each dose to monitor immune cell levels and drug safety throughout the study. Participants will attend multiple clinic visits including screening, dosing visits, and follow-ups. Each dose visit includes blood draws before dosing and at 14 and 30 days after dosing. After completing treatment, participants have three follow-up visits every three months. The study measures adverse events and tracks changes in lymphocyte and immune cell counts up to 60 weeks. Quality of life questionnaires and safety monitoring are also part of participant involvement throughout the trial.

Researchers are evaluating a combination treatment for adults newly diagnosed with Philadelphia Chromosome-positive acute lymphoblastic leukemia PhALL. This phase 2, single-arm, open-label study explores the safety and effectiveness of combining a third-generation tyrosine kinase inhibitor Olverembatinib, a CD3CD19 bispecific T-cell engager Blinatumomab, and a histone deacetylase inhibitor Chidamide, known as the ABC regimen. The study aims to improve early and deep complete molecular remission rates and overall outcomes for this leukemia subtype, especially in patients with high-risk genetic markers like IKZF1 deletions. Participants will receive treatment in phases over several years. Initially, after pretreatment with glucocorticoid, they undergo one year of induction and consolidation therapy with Olverembatinib, Blinatumomab, and Chidamide following a specific schedule of doses and cycles. This is followed by three years of maintenance therapy using Olverembatinib and Chidamide. After treatment, participants enter a five-year follow-up phase to monitor long-term effects and disease status. Throughout the study, participants will be closely monitored for complete molecular remission at three months and other outcomes such as overall survival, event-free survival, and adverse events over up to five years. Specific genetic subgroups like IKZF1del and IKZF1plus will be assessed for treatment response. Regular clinical evaluations, laboratory tests, and safety assessments are part of the study to track participants health and treatment adherence during this multi-year trial.

Researchers are evaluating the safety and activity of sparsentan for treating adult patients with biopsy-confirmed immunoglobulin A nephropathy IgAN, including newly diagnosed patients who have not received prior ACEI or ARB therapy Cohort A and patients with recurrent IgAN after kidney transplantation Cohort B. This open-label, multi-center trial aims to explore sparsentans potential to protect kidney function over an extended period. In Cohort A, patients will start sparsentan at 200 mg daily, increasing to a target dose of 400 mg daily after two weeks if tolerated, with dose adjustments allowed to maintain the highest tolerable dose. Treatment will continue for 110 weeks, followed by a 4-week off-treatment follow-up. Cohort B patients will be randomly assigned to receive sparsentan plus standard care for 48 weeks or standard care alone for 24 weeks before adding sparsentan for the remaining 24 weeks, then followed by a 4-week follow-up. Additional antihypertensive treatments are allowed except for ACEIs, ARBs, aldosterone blockers, or aliskiren. Participants will undergo assessments including urine protein excretion, estimated and measured glomerular filtration rate GFR, kidney biopsy analysis using the Oxford Classification, MRI for kidney and heart function, bioimpedance for body water, and quality of life evaluations. Safety will be monitored through adverse events, lab tests, and vital signs. The primary outcome is urine proteincreatinine ratio at Week 36, with secondary outcomes assessing kidney function, proteinuria changes, and safety over up to 114 weeks.

Researchers are evaluating whether emapalumab or a combination of fludarabine and dexamethasone can effectively prepare people with primary immune regulatory disorders PIRD andor autoinflammatory conditions for stem cell transplants. The study aims to see if these treatments reduce inflammation and help donor stem cells successfully engraft, enabling the immune system to produce fully functioning cells. This is a phase 2 study supported by the FDA Office of Orphan Products Development. Participants are assigned to one of two groups based on their inflammation type. Group A participants with a high CXCL9 cytokine level receive emapalumab on days -22, -15, -8, and -1 before the transplant. Group B participants with generalized inflammation receive fludarabine and dexamethasone for five consecutive days from days -22 to -18. All participants undergo a standard stem cell transplant on day 0 and may receive an additional emapalumab dose within 30 days post-transplant if inflammation markers rise. During the study, participants remain hospitalized according to usual care and have follow-up visits on days 0, 7, 14, 21, 30, 45, 60, 70, 100, 180, 270, and 365, then quarterly for up to three years. Researchers monitor engraftment success, survival rates, graft-versus-host disease incidence, immune recovery, quality of life, and other health outcomes. Data collection continues long-term to assess transplant effects and safety.