Stem Cell Transplantation

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.

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.

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.

This research focuses on kidney transplant patients to collect blood samples and clinical data for developing a non-invasive test that detects donor-derived cell-free DNA (dd-cfDNA) to assess the condition of transplanted kidneys. The study is prospective and multicenter, involving participants who have had a kidney transplant and are undergoing an indication biopsy. The goal is to improve monitoring of the transplanted organ's status. Participants will provide whole blood samples at the time of their indication biopsy, before the biopsy procedure itself. Additionally, leftover de-identified retrospective genomic DNA (gDNA) samples from the kidney donors will be collected for paired analysis. This approach helps researchers study dd-cfDNA in a real-world transplant population. Participants will be involved through blood sample collection and clinical data gathering during their biopsy visits. Researchers will monitor the detection of donor-derived cell-free DNA in whole blood over an 18-month period. The study involves no investigational treatments, focusing on observation and sample analysis. Participation duration and follow-up details align with the biopsy schedule and sample collection requirements.

This research investigates a new self-administered digital application designed to improve sexual health, quality of life, and psychological distress among survivors of hematopoietic stem cell transplants (HCT). HCT survivors often face long-term sexual dysfunction due to complex biological, psychological, and social factors, which significantly affect their well-being and relationships. The study aims to address these challenges through a multidisciplinary approach delivered via a digital platform. Participants will be randomly assigned to either use the SHIFT digital application or receive enhanced usual care. The SHIFT app includes interactive features like gamification, survivor videos, intimacy exercises, and optional content to engage users over eight weeks. Those in the usual care group will meet with their clinicians and may be referred to specialists if needed but will not have access to the SHIFT app. During the study, participants will complete assessments measuring sexual satisfaction, function, quality of life, anxiety, and depression at various points up to 24 weeks. Researchers will monitor global satisfaction with sex at week 8 as the primary outcome. The study involves medical evaluations and tracks psychological and physical health through questionnaires and scales, aiming to evaluate the impact of the digital intervention on sexual health outcomes and overall well-being in HCT survivors.

Researchers are evaluating axatilimab monotherapy in Chinese participants aged 12 years and older who have recurrent or refractory active chronic graft-versus-host disease (cGVHD) after receiving systemic therapy. The study aims to assess the safety, effectiveness, and pharmacokinetics of this treatment in managing cGVHD, a condition that can occur after stem cell transplantation. This is a Phase 1b/2, open-label, multicenter study sponsored by Incyte Corporation. Participants will receive axatilimab through intravenous infusion at protocol-defined doses. The study includes two parts: Part 1 focuses on safety evaluation, and Part 2 assesses efficacy. The treatment duration and dosing schedule follow the study protocol, and participants may continue to receive corticosteroids, calcineurin inhibitors, or mTOR inhibitors if stable. The study will monitor participants for up to two years and 30 days to gather information on treatment responses and adverse events. Throughout the study, participants will undergo various assessments including monitoring for treatment-emergent adverse events, evaluation of response rates, symptom improvement using the modified Lee symptom scale, and pharmacokinetic sampling for axatilimab. Additional laboratory tests will measure changes in immune markers and antibody development. Participants are expected to attend regular visits for these evaluations and safety monitoring during the study period, which may last up to two years and beyond.

Researchers are evaluating tabelecleucel, an off-the-shelf allogeneic T-cell immunotherapy, for treating Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in patients who have undergone solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT) and have not responded to rituximab or rituximab plus chemotherapy. This phase 3, multicenter, open-label study aims to determine the clinical benefit and safety profile of tabelecleucel in these specific patient populations. Participants are divided into cohorts based on transplant type and prior treatments: those with EBV+ PTLD after SOT who failed rituximab alone (with or without chemotherapy), and those with EBV+ PTLD after HCT who failed rituximab. Tabelecleucel is given intravenously in 5-week cycles at a dose of 2 x 10^6 cells/kg on Days 1, 8, and 15, followed by observation until Day 35. Treatment continues until maximal response, unacceptable toxicity, start of other therapy, or failure of tabelecleucel, with limits on the number of different HLA restrictions tested per cohort. Participants undergo extensive assessments including biopsy confirmation, PET-CT or MRI imaging for disease evaluation, and organ function tests. Follow-up for disease and survival status lasts up to 5 years for early enrollees and up to 12 months for others and responders. The primary outcome measured is the objective response rate, with secondary outcomes including duration of response, overall survival, and rates of graft loss or rejection. Safety and efficacy are carefully monitored throughout the study duration.

Researchers are studying the use of abatacept combined with post-transplant cyclophosphamide (PTCy) and bortezomib to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) in adults with blood cancers. The study is conducted in two phases: a phase I dose-escalation to find the maximum tolerated dose of abatacept and a phase II evaluation in two groups based on donor matching. Participants must meet institutional criteria and have matched or partially matched donors. Participants receive a standard conditioning regimen followed by peripheral blood stem cell transplants. Those with unrelated donors also get rabbit anti-thymocyte globulin (rATG). The study drugs—PTCy, bortezomib, and abatacept—are given as GVHD prevention. The phase II dose of abatacept is determined from phase I results. Participants are grouped by donor type: matched sibling, matched unrelated, or mismatched unrelated donors. Throughout the study, participants are monitored for safety and treatment effects, including determining the maximum tolerated dose of abatacept over up to two years. They undergo regular assessments per standard care protocols and study procedures. The study is open-label and non-randomized, with no placebo group. Participants must be available for the full duration and comply with all study procedures.

Researchers are evaluating AC-003 capsules in adults with grade II-IV steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplantation. This Phase Ib, open-label, single-arm study aims to investigate the safety, pharmacokinetics, pharmacodynamics, and early signs of effectiveness of AC-003 in this patient group. The study is conducted at multiple centers and includes approximately 24 participants. The trial consists of two parts. Part A focuses on dose escalation through four sequential cohorts receiving increasing doses of AC-003 orally for 28 days, to determine safety and recommended dosing. Part B involves dose expansion to evaluate preliminary efficacy at the recommended dose, also given orally for 28 days. Safety follow-up occurs on Day 35 after dosing in both parts. Participants will receive specified doses of AC-003 capsules either once or twice daily for 28 days, depending on their cohort. Researchers will monitor safety by recording adverse events up to Day 35 and assess treatment response rates at Days 14 and 28. The study includes pharmacokinetic and pharmacodynamic evaluations, with ongoing safety follow-up and assessments during treatment to measure overall and complete response rates.