Clinical Research Directory

WearAble Technology for Collecting Health Data in People Who Are the Transfused (WATCH Transfused) - A UK Exploratory Study to Improve Quality of Life and the Efficacy of Transfusion Supportive Care in People With Blood Cancers Undergoing Treatment

Cancer treatments such as chemotherapy often affect healthy cells as well as the cancer cells and this can lead to side-effects such as low blood counts - anaemia. This can cause severe fatigue, shortness of breath and brain fog and may need regular blood transfusions. Their quality of life (QoL) is often very poor during treatment because of these side effects, and it is hard to deal with. Doctors use blood tests to decide whether a patient is well enough for treatment and when to start treatment. However, blood tests do not tell us how a person feels, and it is not the same in everyone. We need a better way for doctors to monitor patients' QoL and these symptoms so that they are physically and emotionally able to continue their treatment. It is hard for doctors to accurately assess this through speaking to their patients and doctors do not record or discuss these effects of treatment very well with patients. The aim of this study is to better understand how people feel during their treatment and how we can best use blood transfusions to maintain QoL. 80 adult patients who are starting blood cancer treatments will be asked to answer questionnaires about how they are feeling and their symptoms during their treatment. Participants will be asked to wear a smartwatch to measure their physical activity levels. Activity data collected will then be compared with their reported QoL and blood counts to help us understand when patients can tolerate difficult treatments the best and how blood transfusions affect this. Patients, their family and carers will be invited to take part in an interview to understand their views on how we can improve their care, QoL and access to transfusions. A better understanding of the impact of low blood counts on QoL can help us use blood transfusions to benefit patients' lives. This work will better match transfusions to individual peoples' needs and therefore 'personalise' blood transfusion care.

A Single-arm, Prospective Study of a Cladribine-Bridged LABU Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory MDS/AML in Elderly Patients

Acute myeloid leukemia (AML) is one of the most common hematologic malignancies. With increasing life expectancy and the aging of society, the incidence of AML in the elderly population is rising. The prognosis of elderly AML patients is significantly worse than that of younger patients: the 5-year overall survival rate in patients over 60 years is less than 20%, while the median survival in patients over 80 years is only 3-6 months (1). Improving the overall prognosis of elderly AML has become a hot topic in current hematology research. Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach that involves intravenous infusion of hematopoietic stem cells with the goal of restoring bone marrow and immune function. Although several studies have focused on allo-HSCT in elderly patients, factors affecting transplant outcomes remain controversial, influencing clinical decision-making. Julian et al. retrospectively analyzed 103 elderly patients with relapsed/refractory AML who underwent allogeneic transplantation, showing that high-dose melphalan sequential chemotherapy was effective and well tolerated in elderly AML patients, with a 3-year overall survival rate exceeding 40%; disease prognosis was closely related to donor source and pre-transplant leukemic burden \[2\]. Furthermore, studies on haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly patients are limited. A retrospective analysis from Peking University People's Hospital involving 199 elderly AML patients (≥50 years) who underwent allo-HSCT confirmed that haplo-HSCT is feasible in elderly AML patients; however, transplantation in a refractory/active disease state was associated with poorer transplant outcomes. A study from the EBMT summarized outcomes in 360 elderly patients (≥70 years) who underwent allogeneic transplantation in a non-remission state, reporting 2-year overall survival rates of 25.9%, 43%, and 62.4% for haplo-HSCT, unrelated donor, and matched sibling donor transplants, respectively \[3\]. The challenge in treating relapsed/refractory elderly AML patients lies in improving the tolerability of conditioning regimens and reducing conditioning-related toxicity, thereby increasing the success rate of transplantation. Venetoclax (VEN), an orally administered selective small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, has demonstrated efficacy in randomized clinical trials across several hematologic malignancies. As monotherapy for relapsed/refractory AML, VEN shows modest efficacy while exhibiting good tolerability \[4\]. In the global phase III clinical trial of venetoclax, in newly diagnosed AML patients unfit for intensive induction chemotherapy, venetoclax combined with azacitidine demonstrated significantly superior clinical efficacy compared to azacitidine alone, with a response rate (CR+CRi) more than three times higher than that of the control group, enabling patients to achieve faster and deeper remissions \[5\]. Our center has also accumulated extensive experience with venetoclax in post-transplant maintenance therapy for AML and in the treatment of relapsed/refractory AML \[6-7\]. Additionally, studies have confirmed the safety and efficacy of high-dose venetoclax in newly diagnosed AML \[8\]. Based on the aforementioned clinical efficacy and theoretical rationale, our center previously conducted a study investigating the venetoclax + azacitidine + busulfan (VABu) regimen in allogeneic HSCT for elderly AML patients, confirming that this novel regimen reduces conditioning-related chemotherapy toxicity, improves tolerability, and demonstrates advantages in decreasing cardiotoxicity, mucositis, infections, and organ dysfunction. Lisaftolax, as a second-generation BCL-2 inhibitor, can partially overcome venetoclax resistance and improve patient outcomes. Nevertheless, a consensus on the comprehensive systemic treatment strategy for elderly AML patients has not yet been reached globally. For high-risk or relapsed/refractory elderly AML patients, after risk stratification and assessment of response to chemotherapy, those who are suitable for allo-HSCT may receive a conditioning regimen consisting of cladribine bridged to lisaftolax and busulfan (Clad/LABu), aiming to achieve longer remission duration, reduce post-transplant relapse rates, and improve long-term survival in elderly AML patients.

Luspatercept + Darbepoetin in MDS

This is a single arm open-label Phase II trial of luspatercept and darbepoetin alfa in non-mutated SF3B1 , lower-risk, RBC transfusion dependent MDS participants with an endogenous erythropoietin (EPO) level \< 500 IU/L.

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination. Participants will: * Receive the standard or new drug combination after transplant * Visit the doctor's office for check-ups and tests after transplant that are routine for most transplant patients * Take surveys about physical and emotional well-being * Give blood and stool samples.

A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies

The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.

Romiplostim Versus rhTPO for Platelet Engraftment After Transplant in MDS and AA

This study is for adults aged 18-65 with myelodysplastic syndrome (MDS) or severe aplastic anemia (AA) who are scheduled to receive a donor stem cell transplant (allogeneic hematopoietic stem cell transplant). After the transplant, it is critical for the body to start making its own blood cells again. A common and serious problem is a delay in the recovery of platelets (the cells that help stop bleeding), which increases the risk of bleeding, infection, and death. This study aims to see if a new treatment can help platelets recover faster and more safely after transplant. We are comparing two drugs: Romiplostim: A long-acting injection given just once a week. rhTPO (Recombinant Human Thrombopoietin): A standard injection given every day. Both drugs are designed to help the body make more platelets. The main question is whether the once-weekly romiplostim works as well or better than the daily rhTPO, and if it is safe. About 66 patients will participate. By random chance (like flipping a coin), each participant will be assigned to receive either romiplostim or rhTPO. The treatment will start a few days after the transplant and continue until platelets recover to a safe level or for up to 8 weeks. Doctors will closely monitor all participants for 100 days to track platelet recovery, need for transfusions, side effects, and overall health.

Romiplostim N01 for Platelet Recovery After Haploidentical HSCT

This is a prospective, randomized, controlled clinical study designed to evaluate the efficacy and safety of Romiplostim N01 in promoting platelet engraftment after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in patients with hematologic malignancies. A total of 130 patients who undergo haplo-HSCT for acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or other hematologic malignancies will be enrolled and randomized 1:1 into a treatment group and a control group. The treatment group will receive Romiplostim N01 subcutaneously once weekly at a starting dose of 5 µg/kg, with dose adjustments based on platelet counts (maximum 10 µg/kg), for up to 4 weeks or until platelet counts reach ≥100 × 10⁹/L. The control group will not receive rh-TPO or any thrombopoietin receptor agonist (TPO-RA) therapy. Supportive care including transfusions and growth factors (G-CSF, ESA) is allowed in both groups. The primary endpoint is the cumulative platelet engraftment rate by day +21 post-transplant, defined as sustained platelet counts \> 20 × 10⁹/L for at least 7 consecutive days without transfusion. Secondary endpoints include median time to platelet engraftment, median time to achieve platelet counts ≥ 50 × 10⁹/L and ≥ 100 × 10⁹/L, total platelet transfusion volume, erythroid and neutrophil responses within 4 weeks, and overall hematopoietic recovery. Safety endpoints include the incidence of adverse events, thromboembolic events, and treatment-related serious adverse events. The study aims to determine whether early administration of Romiplostim N01 can accelerate platelet recovery and reduce bleeding risk in patients undergoing haplo-HSCT, thereby improving post-transplant outcomes.

A Phase 1 Study of CG009301 for Injection in Adult Subjects With Recurrent or Refractory Haematological Malignancies

The goal of this clinical trial is to learn about the safety of drug CG009301. It also learns if drug CG009301 works to treat in Participants with relapsed or refractory adult haematological malignancies. The main question\[s\] it aims to answer are: 1. To determine the maximum tolerated dose (MTD) and/or objective best dose (OBD) of CG009301 for injection in subjects with relapsed or refractory adult haematological malignancies. 2. To establish subsequent dosing regimens for CG009301 for injection. 3. To characterise the safety profile and tolerability of CG009301 for injection. Participants will Receive treatment with CG009301 until disease progression.

Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells

Background: * Stem cell transplants from related donors (allogenic stem cell transplants) can be used to treat individuals with certain kinds of severe blood diseases or cancers, such as severe anemia. Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient. Because stem cell transplants can have serious complications, researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications. * By reducing the number of white blood cells included in the blood taken during the stem cell collection process, and replacing them with a smaller amount of white blood cells collected prior to stem cell donation, the stem cell transplant may be less likely to cause severe complications for the recipient. Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications. Objectives: \- To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient. Eligibility: * Recipient: Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants. * Donor: Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood. OR unrelated donors found through the National Marrow Donor Program. Design: * All participants will be screened with a physical examination and medical history. * DONORS: * Donors will undergo an initial apheresis procedure to donate white blood cells. * After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood. * After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood. * RECIPIENTS: * Recipients will provide an initial donation of white blood cells to be used for research purposes only. * From 7 days before the stem cell transplant, participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and anti-thymocyte globulin to suppress their immune system and prepare for the transplant. * After the initial chemotherapy, participants will receive the donated white blood cells and stem cells as a single infusion. * After the stem cell and white blood cell transplant, participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells. Participants will have three doses of methotrexate within the week after the transplant, but will continue to take cyclosporine for up to 4 months after the transplant. * Participants will remain in inpatient care for up to 1 month after the transplant, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.

Safety and Feasibility of Sulforaphane to Promote Early Haematopoietic Recovery After Cord Blood Transplantation

Umbilical cord blood (UCB) is rich in haematopoietic stem progenitor cells and immune cells, and is used for transplantation for a variety of haematological disorders with the advantages of low mating requirements and fewer transplant complications. By March 2025 China's seven (eight) public cord blood stem cell banks had frozen more than 280,000 public umbilical cord blood, while the percentage of those frozen for ≥10 years was 26%, making clinical application a concern. The previous study showed that long-term freezing impairs cellular mitochondrial function leading to decreased reconstruction of cord blood haematopoietic stem progenitor cells and impaired differentiation into the megakaryotic lineage, and that intervention with the antioxidant radicicol thiols (SFN) can partially rescue the cellular functional damage caused by freezing. The findings were based on immunodeficient animals, and clinical studies are urgently needed to determine whether SFN intervention can promote post-transplant haematopoietic reconstitution in patients with long term cryopreserved (≥10 years) UCB. In this project, the investigators propose to conduct a single-arm, open, single-centre phase I-II clinical study on the safety and feasibility of dietary supplement SFN to promote early haematopoietic restoration after cord blood transplantation to evaluate the safety and feasibility of the use of long-frozen UCB for peri-infusion SFN use in adult transplant recipients, and to reveal the effect of peri-infusion SFN use on neutrophil implantation. This project will provide scientific guidance to promote the clinical application of long-term cryopreserved UCB, as well as key data to optimise the clinical transplantation strategy of UCB and expand its application.

Clinical Study of ARD103 CAR-T Therapy for Patients With R/R AML or MDS

This is a phase I/2, interventional, open-label, multicenter study to assess the safety and efficacy of ARD103 in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.

A Long-term Follow-up Study of Patients With ARD103 CAR-T Cell Therapies

This study will evaluate the long-term safety of ARD103 cellular therapies

Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning Before Allogeneic Stem Cell Transplantation

Safety and Feasibility of a Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning Before Allogeneic Stem Cell Transplantation in AML, MDS/AML and Higher Risk MDS

Evaluation of Treosulfan Versus Melphalan Conditioning Followed by PTCy in Patients With AML and MDS Undergoing Allogeneic Transplantation

The aim of this study is to compare the effectiveness and tolerability of two conditioning chemotherapies prior to allogeneic stem cell transplantation. The following will also be investigated: * Survival * Remission and Relapse rate * Engraftment or graft failure * Graft versus Host Disease (GvHD)

Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT

The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.

Anti-NKG2A Monoclonal Antibody for AML or MDS Patients Undergoing Haploidentical Transplantation

The goal of this clinical trial is to evaluate the effectiveness and safety of the anti-NKG2A monoclonal antibody (Monalizumab) in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The main questions this trial aims to answer are: * Does Monalizumab improve graft-versus-host disease-free and progression-free survival (GPFS) in patients after Haplo-SCT? * What are the safety and side effects of Monalizumab in this patient group? * How does Monalizumab affect the reconstitution and function of NK cells in patients undergoing Haplo-SCT? * Researchers will administer Monalizumab to participants on day +30 and +44 after transplantation to see if it enhances immune responses and prevents disease relapse or GVHD. Participants will: * Receive Monalizumab intravenously at 1 mg/kg on day +30 and day +44 after Haplo-SCT * Be monitored for clinical outcomes such as GVHD, survival rates, and immune function for up to one year after the transplant * Undergo regular checkups and tests to assess the effectiveness and safety of the treatment