Clinical Research Directory

Expanded Donor Stem Cells for Poor Graft Function After Stem Cell Transplantation in Children

Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT) and may cause persistent low blood cell counts despite donor-cell engraftment. This single-center, open-label, Phase I pilot study will enroll three children aged 6-18 years with PGF after allogeneic HSCT who have not responded adequately to conventional hematopoietic supportive treatments. CD34-positive hematopoietic stem cells will be collected from each participant's original related transplant donor and expanded outside the body for \~10 days using the small-molecule compound HEB-001 together with the cytokines stem cell factor, thrombopoietin, and FLT3 ligand. The expanded cells will then be administered as a single intravenous infusion. The main objectives are to assess acute infusion-related adverse events during the first 30 days and to examine genetic stability through 1 year. Preliminary hematopoietic recovery will be assessed using neutrophil and platelet recovery and donor chimerism. All participants will receive the investigational cell infusion; there is no comparator group.

Decitabine for Poor Graft Function Post Allo-HSCT

This randomized trial aims at validating the efficacy and safety of low-dose decitabine for PGF post allo-HSCT.

Anakinra for Prevention of Poor Graft Function in MDS Allo-HSCT

Preclinical evidence indicates that IL-1 inflammatory signaling suppresses bone marrow mesenchymal stromal cells (MSCs) from secreting stem cell factor (SCF), leading to failure of their hematopoietic supportive capacity, and that the interleukin-1 receptor antagonist (IL-1Ra, Anakinra) can reverse this process. Sustained low-level IL-1 signaling also drives hematopoietic stem cell (HSC) dysfunction, including progression of clonal hematopoiesis and transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A prior phase 2 trial of IL-1 inhibition in lower-risk MDS demonstrated hematologic improvement without an increased risk of leukemic transformation. Based on these findings, this study hypothesizes that early administration of Anakinra after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS, by inhibiting IL-1β signaling, improving the bone marrow microenvironment, and reducing the occurrence of poor graft function (PGF), does not increase the risk of post-transplant relapse. The study comprises two parts: a dose-escalation phase to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of Anakinra in post-allo-HSCT patients, and an efficacy-validation phase to evaluate the preventive effect of Anakinra at the RP2D on PGF.

CD34+ Selected Stem Cell for Poor Graft Function or Graft Failure

The proposed trial is a single arm, non-randomized, single center pilot study utilizing CliniMACS CD34 Reagent System for patients following allogeneic hematopoietic stem cell transplant (HSCT) requiring treatment of graft dysfunction or failure.

The Safety and Efficacy of Umbilical Cord Blood Mononuclear Cells in Patients With Secondary Poor Graft Function After Hematopoietic Stem Cell Transplantation

This study is conducted in a prospective, single-center clinical design and is divided into two stages: dose escalation and dose extension. Patients meeting the diagnostic criteria of secondary poor graft function are selected as the study objects. The safety data of umbilical cord blood mononuclear cells in the treatment of secondary poor graft function are obtained through dose escalation stage, and then one dose is selected for dose extension stage to explore the efficacy of umbilical cord blood mononuclear cells in treating secondary poor graft function.

REscuing Bone Marrow Function in Patients with AplaStic AnaEmia and Bone Marrow FaiLure Post AllogEneiC Transplantation 2

Allogeneic stem cell transplantation involves the transplanting of donor blood stem cells into a recipient, this is performed mainly for the treatment of blood cancers. The bone marrow is the organ that produces all blood cells and allogeneic stem cell transplantation results in the replacement of abnormal recipient bone marrow with donor blood cells as well as the production of donor immune cells from the donor bone marrow. The production of donor immune cells will hopefully lead to an immune response directed at any persisting cancerous cells leading to their eradication. As such, one of the key measures of success of a transplant is establishment of donor engraftment. Engraftment is considered successful when the patient has normal blood cell counts on routine laboratory testing as well as confirmation that the blood cells are being produced by donor bone marrow cells. Confirming donor blood cell production is done by a process called chimerism. Poor graft function (PGF) is a complication of allogeneic stem cell transplantation related to engraftment, manifested by low blood counts despite complete donor chimerism. This has significant consequences for the patient leaving them susceptible to infection because of low white blood cells and bleeding because of low platelets (the cell components that are important for blood clotting). There is currently no established treatment for this condition and patients with this condition who do not recover have a poor survival. Aplastic anaemia (AA) is a rare autoimmune condition that results in a patient's own immune system attacking important components of their bone marrow resulting in low blood counts. The current treatments for AA include suppressing the immune system or a bone marrow transplant, however long term survival for patients who do not respond to these treatments or relapse is poor and more effective treatments are required. There is emerging evidence that demonstrates that the components of the immune system are dysfunctional and result in excessive immune activation resulting in suppression of the bone marrow characteristic of PGF. Similar features of immune dysfunction has been demonstrated in AA. Ruxolitinib is a drug that may be able to reduce this excessive immune activation. Eltrombopag is a drug that has been shown to stimulate the production of blood cells. The aim of this study is to evaluate whether the combination of ruxolitinib and eltrombopag is safe and effective in the treatment of PGF and AA.

Mesenchymal Stem Cell Infusion as Treatment for Steroid-Resistant Acute Graft Versus Host Disease (GVHD) or Poor Graft Function

The present project aims at investigating the role of MSC for the treatment of patients with Part 1: Steroid-refractory grade II-IV acute GVHD. Part 2: Poor graft function (PGF) Part 3: Low or falling donor T-cell chimerism after allogeneic HCT. This is a multicenter phase II study examining the feasibility and efficacy of this approach.

Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT

This randomized trial aimed at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients.