Graft-Versus-Host Disease (GVHD)

Researchers are studying the immunologic changes on the surface of the eye in cancer patients, focusing especially on those with ocular graft-versus-host disease (oGVHD). This observational, natural history study aims to understand risk factors, mechanisms of eye damage, drug targets, and effects of oGVHD on the eye over a period of up to four years. Two groups will participate: cancer patients scheduled for bone marrow transplant, who will be evaluated every three months for two years, and healthy control patients without eye disease or cancer history, who will be evaluated every six months. During each visit, standard eye exams will be performed alongside collection of biological specimens such as ocular surface wash, mucocellular material, corneal filaments, impression cytology of conjunctiva, blood, or serum. Participants will attend periodic study visits for clinical exams and specimen collection while receiving their usual care. Researchers will assess various factors including eye disease risk, mechanisms of eye damage, and ocular effects of graft-versus-host disease. The study involves repeated evaluations and biological sampling to track changes over time, with a maximum follow-up of four years.

Researchers are investigating acute myocardial inflammation, a complex condition that includes acute cellular cardiac allograft rejection (ACR), cardiac sarcoidosis (CS), and immune checkpoint inhibitor induced myocarditis (ICIM). This study aims to evaluate the accuracy of [68Ga]Ga-PentixaFor PET/CT imaging for detecting inflammatory cells in these patients, offering a potentially non-invasive diagnostic option. The study is a phase 2 trial focusing on these specific heart inflammation conditions where diagnosis is currently challenging. Participants will receive an intravenous injection of a maximum of 50 micrograms of PentixaFor labeled with 150 ±15 MBq of Gallium-68 ([68Ga]) as a bolus 60 ±15 minutes before undergoing PET/CT imaging. The treatment involves this imaging procedure for all three patient groups (ACR, CS, ICIM) to assess the presence and characteristics of myocardial inflammation. During the study, researchers will evaluate imaging results by analyzing lesion number, location, and standardized uptake value (SUV) over one year. They will also monitor toxicity data for safety assessment. Participants will have regular clinical follow-ups at the cardiology department. The study involves signing informed consent and includes monitoring for any adverse effects related to the imaging agent or procedures throughout the study duration.

Researchers are investigating the specific targets of T cells involved in autoimmune diseases by studying tissues from patients with active organ inflammation caused by autoimmune conditions. The study aims to identify which T cells are activated and expanding in diseased tissues compared to blood or normal tissues. This information will help discover new peptide targets and their associated T cell receptors (TCRs) to develop potential new therapies for autoimmune diseases. Participants will provide tissue samples and matched blood samples during clinical procedures such as endoscopy, arthrocentesis, lumbar puncture, skin biopsy, bronchoscopy, or surgery, depending on their autoimmune condition. The study includes several groups covering diseases like Crohn's disease, ulcerative colitis, celiac disease, ankylosing spondylitis, multiple sclerosis, scleroderma, systemic sclerosis, and other autoimmune diseases. Samples may come from excess clinical materials or research-specific biopsies, with the possibility of serial sampling over time. During the study, participants will undergo standard clinical procedures with collection of additional tissue or fluid samples and companion blood draws. Researchers will analyze these samples to identify peptide targets linked to disease-reactive T cells over a period of up to three years. The study includes comprehensive assessments of tissues and blood to understand T cell activity in autoimmune disorders, with monitoring of participant safety and no interventions beyond routine clinical care.

Researchers are evaluating the safety and effectiveness of GT729 universal cell injection for treating patients with refractory or relapsed chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation. This early phase 1 clinical trial aims to understand how this biological treatment affects people who have not responded to at least two prior systemic therapies for active cGVHD. Participants will receive the GT729 injection as the experimental treatment. The study will monitor participants from the time of infusion through 24 months to assess safety outcomes such as dose limiting toxicity within 28 days and the occurrence of adverse events. Researchers will also evaluate the overall response rate up to 6 months after the infusion. During the study, participants will undergo regular assessments including laboratory tests to monitor blood counts, liver and kidney function, and pregnancy status for women of childbearing age. Safety and treatment response will be closely observed throughout the treatment period. The total participation duration may last up to two years for long-term safety monitoring and outcome evaluation.

Researchers are evaluating the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed or refractory B-cell related autoimmune diseases. This early phase 1 pilot study plans to enroll 15 patients to assess the treatment's safety, feasibility, and effectiveness. The study also explores how well KN5501 expands, persists, and depletes CD19 positive B cells in these patients. Participants will receive a preparatory treatment with Fludarabine and Cyclophosphamide on three days before the infusion of anti-CD19 CAR NK cells. The trial includes two dose levels (6x10^9 and 9x10^9 cells) for dose escalation. This is a single-arm, open-label study without a placebo group. During the study, researchers will monitor participants closely for dose limiting toxicities and adverse events within the first 4 weeks and at 12, 24, 36, and 52 weeks after infusion. Effectiveness will be evaluated by disease control and remission rates at the same time points. Participants will undergo regular assessments including clinical evaluations and laboratory tests, with follow-up lasting up to one year after treatment.

Thalassemia is a common inherited blood disorder, particularly prevalent in Yunnan, China, where many patients face high treatment costs. Current treatments include blood transfusions and hematopoietic stem cell transplantation (HSCT), which can cure thalassemia but involve significant risks and complications such as organ damage and graft-versus-host disease (GVHD). This research explores a new approach called hypertransplantation, developed by Professor Ai Huisheng's team, aiming to provide a safer, more effective, and affordable treatment without the need for pre-treatment or causing GVHD. The study will test hypertransplantation, which uses hematopoietic stem cells from haplotype-compatible healthy donors without requiring pre-treatment such as chemotherapy or radiation. This innovative method relies on immune interactions between donor and recipient to achieve stable donor cell implantation. Animal studies showed promising results with no GVHD or reproductive damage, and this clinical trial plans to enroll 3 to 5 patients aged 7 to 12 years with severe Mediterranean thalassemia who are ineligible or refuse standard HSCT or gene therapy. Participants will receive the hypertransplantation treatment and be closely monitored for donor cell implantation, blood counts, hemoglobin levels, immune function, and potential complications like infections or GVHD. The primary outcome will be the donor cell implantation rate three months after transplantation, with secondary outcomes including gene carrier status after one year. The study involves a single center and a single treatment group, with follow-up assessments to evaluate safety, efficacy, and recovery of endocrine and gastrointestinal functions over time.

This trial is investigating the use of TQ05105 Tablets in adults aged 18 to 70 with moderate to severe chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation. The study aims to evaluate the efficacy and safety of this oral medication, which targets inflammatory and fibrotic processes involved in cGVHD. The trial is open-label and multicenter, sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., and conducted as a Phase II clinical study. Participants receive TQ05105 Tablets twice daily in 28-day treatment cycles. The study measures responses up to 48 weeks, including treatment effectiveness and safety outcomes. The primary outcome is the objective response rate at 24 weeks. Secondary outcomes include duration of response, survival rates, incidence of relapse, and adverse events. The study does not involve placebo or blinding. During their participation, patients will be monitored regularly with assessments to track their response to treatment, side effects, and overall health status. Evaluations include laboratory tests and clinical examinations related to cGVHD severity and treatment impact. The total participation period extends up to 48 weeks or more, with ongoing observation for safety and survival measures. Participants will follow a stable medication regimen and adhere to contraceptive measures if applicable.

Researchers are conducting a prospective observational study to explore the relationship between autonomic nervous system (ANS) function and acute graft-versus-host disease (GvHD) in patients who undergo allogeneic hematopoietic stem cell transplantation. The study aims to use ANS function measurements as early tools for classification and assessment in transplant recipients. This research is led by the Institute of Hematology & Blood Diseases Hospital in China. Participants in this study are adult patients receiving HLA-haploidentical stem cell transplants. Various tests will be conducted before and after transplantation, including heart rate response to standing, piloerection tests, and dynamic electrocardiography to evaluate ANS function. These assessments take place within one month before transplantation and again between 17 to 25 days after transplantation. The study also monitors the incidence of acute GvHD, including severe cases, within 100 days after transplantation. During the study, participants will undergo scheduled evaluations to measure heart rate response, piloerection, and electrocardiography changes. Researchers will track these physiological responses to understand their association with the development of acute GvHD. The study period includes monitoring up to 100 days post-transplant to assess disease outcomes. Participants are expected to provide informed consent and comply with study monitoring requirements throughout the observation period.

Patients who need an allogeneic hematopoietic cell transplant (HCT) face the risk of developing graft-versus-host disease (GVHD). To reduce this risk, one approach uses ex vivo alpha-beta T-cell depletion of donor cells. The CliniMACS Device, approved by the FDA for a limited use, can process these cells, but other uses require research protocols. This study explores the feasibility of using the CliniMACS system for alpha-beta T-cell depletion in stem cell transplant recipients to better understand its application beyond approved indications. The CliniMACS CD34 Reagent System uses antibodies linked to magnetic particles to select blood stem cells (CD34+ cells) from donor samples. In this study, stem cell products depleted of alpha-beta T-cells using the CliniMACS system are infused intravenously at a rate based on body weight. The aim is to deliver a target dose of CD34+ cells and minimize alpha-beta T-cell numbers to reduce the risk of GVHD. This approach also includes simultaneous depletion of CD19+ B cells. The study evaluates this method as an alternative to traditional CD34-selection techniques. Participants will receive the alpha-beta T-cell depleted stem cell infusion and be monitored for outcomes including the incidence of severe acute GVHD within 100 days. Other assessments include engraftment success, transplant-related mortality, chronic GVHD requiring steroids, autoimmunity needing immunosuppressive treatment, and T-cell immune recovery over the first year after transplant. Safety and effectiveness of the procedure are followed up to one year, with the total participation duration varying accordingly.

Researchers are collecting long-term safety and effectiveness data for participants treated with ibrutinib, a first-in-class, orally taken medicine that targets Bruton’s tyrosine kinase. The study focuses on individuals who have already been treated with ibrutinib in prior studies and are continuing to benefit from the treatment. The goal is to provide ongoing access to ibrutinib while monitoring health outcomes over time. Participants will continue taking ibrutinib capsules once daily at the dose established in their previous study (ranging from 140 mg to 560 mg) until the doctor decides the treatment is no longer helping, the participant chooses to stop, or other specified reasons occur. Some participants may receive ibrutinib alone or in combination with nivolumab depending on their prior treatment. The study is open-label, meaning everyone knows the treatment being given. During the study, participants are regularly monitored for safety and disease changes through assessments and visits until they stop the study drug or move to other treatments. Researchers track side effects up to 30 days after the last dose and may analyze how the disease responds in combination with earlier study data. The study continues until all participants transition off study treatment or the sponsor ends the trial, ensuring ongoing care and data collection over time.