Primary Immunodeficiency

Researchers are studying the long-term effects of reducing household air pollution (HAP) from biomass fuel use on heart, lung, and immune health among women and children in semi-rural Bangladesh. The study evaluates whether a mobile phone-based behavioral change communication (mHealth BCC) intervention can increase the adoption and exclusive use of cleaner cooking fuel, Liquid Petroleum Gas (LPG). This research also investigates how lowering pollution exposure might influence immune responses to vaccines and subclinical cardiovascular and pulmonary changes. The study is a large household-level randomized controlled trial comparing two groups: one receiving the mHealth BCC intervention encouraging exclusive LPG use and a control group receiving no such intervention. Researchers will monitor personal and area levels of air pollutants like PM2.5 and black carbon before and after intervention, alongside detailed assessments including spirometry, chest X-rays, high-resolution CT scans, blood pressure, EKG, metabolic markers such as HbA1c and lipid profiles, and immune cell function. The intervention messages are delivered via mobile phone with frequency tailored to participant responses. Participants will be followed over two years with repeated measurements to assess pollutant exposure and health effects. Evaluations include lung function tests, imaging, cardiovascular markers, metabolic blood tests, and immune function assays. The study aims to provide insights into the health benefits of sustained LPG use and improved air quality. Total participation spans pre-intervention assessments through two years of follow-up, with ongoing monitoring of pollution exposure and health outcomes.

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 0/1 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.

This research aims to evaluate the safety of Immune Globulin Subcutaneous (Human), 20% Solution in people with primary immunodeficiency diseases (PID) using data from a medical database in Japan called PIDJ2. The study is observational and involves reviewing existing patient records to learn about the treatment's safety in this group. It is sponsored by Takeda and focuses on important safety concerns related to this treatment. Participants included in the study are those with PID who have received the Immune Globulin Subcutaneous (Human), 20% Solution according to the treatment guidelines. The study collects data retrospectively from the PIDJ2 registry, which tracks patients over time. The treatment was given as an infusion following the approved package instructions. Participants' medical records will be reviewed to identify any adverse events such as anaphylactic reactions, thromboembolism, or aseptic meningitis occurring from the start of treatment up to five years. This long-term safety monitoring uses the registry data without new treatment or visits. The study period extends through July 2030, focusing on real-world safety outcomes for people with PID receiving this therapy.

Researchers are studying the use of unlicensed cryopreserved cord blood units (CBUs) for transplantation in both pediatric and adult patients with various blood-related cancers and other disorders affecting the blood-forming system. This observational study aims to evaluate outcomes such as the recovery of a certain level of white blood cells after transplantation, as well as the incidence of infections, infusion reactions, survival rates, and graft-versus-host disease over time. The study involves patients receiving unlicensed CBUs at multiple U.S. transplant centers. These CBUs are used for patients with hematologic malignancies and other blood disorders. The protocol collects data on patients who receive these unlicensed transplant units, without administering a new treatment but observing the outcomes after transplantation. Participants will be monitored for neutrophil recovery at 60 and 100 days post-transplant, along with assessments of infection transmission, infusion reactions, survival one year after transplant, and occurrences of acute and chronic graft-versus-host disease. Platelet engraftment levels will also be tracked. The study includes patients of any age and follows them through the transplantation and recovery process to gather information on these key outcomes.

Researchers are studying pyrimidine and purine metabolism disorders (DPPMs), which affect how the body processes certain chemicals and can cause a range of symptoms from mild to severe, impacting the brain, blood, kidneys, and immune system. This research aims to better understand the causes, features, and outcomes of these disorders by comparing affected individuals, their unaffected family members, and healthy volunteers. The study focuses on both known and novel DPPMs and seeks to identify genomic, clinical, pharmacological, laboratory, and dietary factors influencing disease variability. Participants are divided into three groups: those diagnosed with DPPMs, their family members without the disorder, and healthy volunteers. Affected participants visit the clinic at least once a year, undergoing physical exams, sample collections (blood, urine, saliva, stool), and various tests depending on symptoms, which may include skin and mouth swabs, heart, kidney, brain, and nerve function tests, dental, hearing, and vision exams, learning assessments, physical activity monitoring, imaging scans, and photographs. These evaluations may be spread over up to seven days, and affected participants may remain in the study indefinitely. Family members and healthy volunteers have a single study visit with a physical exam and sample collections. Throughout the study, researchers collect DNA and biological samples for genetic, biochemical, enzyme, and microbiome analyses. The study includes detailed clinical and laboratory assessments to track disease features and variability. Participants' medical, laboratory, and imaging data are collected following standard care protocols. The primary outcome is to describe features of poorly characterized DPPMs, while secondary outcomes focus on identifying factors associated with different clinical results. The study involves long-term monitoring and may continue indefinitely for affected individuals.

Researchers are investigating the use of allogeneic hematopoietic stem cell transplantation (HSCT) to treat VEXAS Syndrome, a newly identified disease characterized by inflammatory and blood-related problems. This syndrome involves symptoms such as fever, skin lesions, and bone marrow failure, often resistant to standard treatments. The study aims to determine if HSCT can successfully replace the patient's bone marrow with donor cells and improve or reverse the disease's clinical features over time. Participants will receive a stem cell transplant from a matched or haploidentical donor after undergoing a reduced intensity conditioning regimen tailored to the donor match type. This includes drugs like fludarabine, busulfan, cyclophosphamide, and possibly low-dose total body irradiation. After the transplant, participants will receive medications such as mycophenolate mofetil and tacrolimus to prevent graft-versus-host disease. The transplant is given via a central venous catheter, and participants must stay near the hospital for at least 100 days with frequent follow-up visits. During the study, participants will undergo extensive screening including physical exams, imaging scans, blood and urine tests, bone marrow biopsies, and specialist consultations. Post-transplant, they will attend scheduled visits up to two years after receiving the transplant to monitor donor cell engraftment, disease reversal, safety outcomes, and any complications like graft-versus-host disease. The study includes yearly follow-ups by phone after two years, with total participation possibly extending beyond three years.

Researchers are studying idiopathic CD4 lymphopenia (ICL), a condition where people have low levels of CD4 T cells, making them vulnerable to infections, autoimmune diseases, and cancers. The study aims to test a new drug called NT-I7 (efineptakin alfa) that may increase CD4 T cell counts in people with ICL. This open-label trial is sponsored by the National Institute of Allergy and Infectious Diseases and focuses on evaluating the safety and immune effects of NT-I7 in adult participants with ICL. Participants will receive three doses of NT-I7 by injection into the muscle of the upper arm, thigh, or buttock, spaced about 12 weeks apart over a 24-week period. The study involves three dose levels based on body weight: 240, 480, or 720 micrograms per kilogram. Alongside dosing, participants will undergo leukapheresis three times to collect and separate white blood cells. Some visits may include rectal swabs, skin exams, biopsies, and medical imaging as part of the assessments. Throughout the study, participants will have physical exams and blood tests before each dose and at follow-up visits up to week 60. Blood samples will be collected regularly to monitor immune cell counts and safety. Questionnaires will assess patients' health perceptions and quality of life. After the final dose, participants will have three follow-up visits every three months to continue monitoring safety and immune responses. The primary outcome is the number and severity of side effects related to NT-I7, assessed at week 60.

Researchers are evaluating a combination treatment for adults newly diagnosed with Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ALL). This phase 2, single-arm, open-label study explores the safety and effectiveness of combining a third-generation tyrosine kinase inhibitor (Olverembatinib), a CD3/CD19 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 sparsentan's 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 protein/creatinine 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) and/or 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.