Clinical Research Directory

A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies

The purpose of this study is to examine if it is feasible to administer decitabine and filgrastim after allogenic hematopoietic stem cell transplant (HCT) in children and young adults with myelodysplastic syndrome, acute myeloid leukemia and related myeloid disorders, and if the treatment is effective in preventing relapse after HCT. The names of the study drugs involved in this study are: * Decitabine (a nucleoside metabolic inhibitor) * Filgrastim (a recombinant granulocyte colony-stimulating factor (G-CSF)

Fludarabine Plus Melphalan Versus Addition of Venetoclax to Fludarabine/Melphalan Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in AML/MDS Patients Aged > 50 Years: a Multicenter, Randomized, Phase 3 Trial

Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) serves as a curative treatment modality for the vast majority of patients with hematological malignancies. Historically, due to the relatively high treatment-related mortality rate associated with Allo-HCT, this therapy was primarily administered to younger patients. However, the median age at onset of most hematological malignancies falls within the elderly population. For instance, the median ages at onset of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are 68 and 77 years, respectively. In recent years, with the advancement of transplantation techniques and the application of Reduced-intensity Conditioning (RIC) regimens, a growing number of elderly patients have undergone Allo-HCT. Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) indicate that in 2017, 31% of patients who received Allo-HCT were aged over 60 years, and 6% were over 70 years old. Over the past decade, the number of elderly patients undergoing Allo-HCT has increased significantly. Given that most elderly patients cannot tolerate conventional myeloablative conditioning regimens, RIC regimens based on Fludarabine (Flu) combined with Busulfan (Bu), or Fludarabine (Flu) combined with Melphalan (Mel) are currently widely used in elderly patients undergoing Allo-HCT. Nevertheless, the post-transplant relapse rate remains as high as 30%-55%, and the long-term GVHD-free and Relapse-free Survival (GRFS) rate fluctuates between 21% and 59%, suggesting that the efficacy of transplantation needs to be further improved. Further comparison of the commonly used RIC regimens in elderly patients-namely Flu+Bu (2-day), Flu+Bu (4-day) and Flu+Mel-has demonstrated that the Flu+Mel regimen yields superior transplantation outcomes over the Flu+Bu regimens. At present, the optimal RIC regimen for elderly patients with hematological malignancies has not yet been clearly defined. The selection of transplantation conditioning regimens for elderly patients should strike a balance between reducing non-relapse mortality and decreasing post-transplant relapse. Over the past 20 years, an increasing number of targeted drugs acting on specific cellular signaling pathways, anti-apoptotic proteins, epigenetic regulators, and monoclonal antibodies have been introduced into clinical practice, thereby revolutionizing the treatment landscape of hematological malignancies. These novel targeted therapies not only bring hope of achieving remission to patients with hematological tumors resistant to traditional chemotherapy, but also the combined application of novel drugs and Allo-HCT is bound to fundamentally transform the overall technical system of hematopoietic stem cell transplantation. Venetoclax is a potent and selective oral inhibitor targeting the BH3 domain of the anti-apoptotic protein Bcl-2. In 2018, the FDA approved Venetoclax as a first-line induction chemotherapy agent for elderly AML patient's ineligible for intensive chemotherapy, with a complete remission rate of up to 67% and favorable tolerability¹¹. Preclinical studies using Allo-HCT animal models have confirmed that the addition of a Bcl-2 inhibitor to RIC regimens can promote donor cell engraftment, reduce the incidence of GVHD, without impairing the graft-versus-leukemia (GVL) effect¹². In recent years, clinical trials have reported the efficacy and safety of the conditioning regimen combining Venetoclax with Flu+Bu in patients with myeloid malignancies undergoing Allo-HCT. Our research center has demonstrated the favorable safety profile and promising long-term survival outcomes of the Venetoclax plus Flu+Mel conditioning regimen in a phase II clinical trial involving patients aged over 50 years with AML/MDS undergoing Allo-HCT (2024 EBMT Poster B093; 2025 EBMT Poster B126). However, the long-term superiority of this novel regimen over the conventional Flu+Mel conditioning regimen remains to be clarified. Therefore, based on the existing findings from clinical studies and Allo-HCT animal model research, we hypothesize that incorporating Venetoclax into the Fludarabine+Melphalan conditioning regimen for elderly patients undergoing Allo-HCT is expected to improve long-term post-transplant survival and further enhance the transplantation efficacy in this patient population.

A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies

The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied.

A Phase II Open-label Study of Olutasidenib Post-transplant Maintenance Therapy for Patients With IDH1-mutated Myeloid Malignancies

The goal of this clinical research study is to learn about the safety and tolerability of giving olutasidenib to patients with IDH1-mutated myeloid malignancies as maintenance therapy after they receive a stem cell transplant.

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS.

VEN+DAC+Bu2Flu4 vs Bu2Flu5 Conditioning Regimen for Elderly Myeloid Malignancies Undergoing Allo-HSCT

The purpose of this study is to compare the efficacy and safety of venetoclax+decitabine+busulfan+fludarabine (VEN+DAC+Bu2Flu4) regimen with busulfan+fludarabine (Bu2Flu5) regimen in older patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Exploratory Clinical Study on the Safety and Efficacy of CAR-T Cell Therapy in the Treatment of Relapsed/Refractory Myeloid Malignancies

This is an open-label, single-arm, exploratory clinical trial utilizing a "3+3" dose escalation followed by dose expansion to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of CD33/CD123/CLL-1 CAR-T cell therapy in patients with relapsed/refractory myeloid malignancies. Part A: Dose Escalation Phase. Follows a "3+3" dose escalation design with four predefined dose cohorts: 0.2×10⁶, 0.5×10⁶, 1×10⁶, and 2×10⁶ CAR-positive cells/kg.Anticipated enrollment: 12-24 subjects.Primary objectives: Assess safety, tolerability, and determine MTD.Dose-limiting toxicity (DLT) observation period: 28 days post-infusion. Part B: Dose Expansion Phase.Enrolls 21 additional subjects to receive CAR-T cell infusion at the recommended Phase 2 dose (RP2D) established in Part A.Primary objective: Further evaluate therapeutic efficacy. Overall Study Objectives:Safety profile of CD33/CD123/CLL-1 CAR-T therapy.Efficacy endpoints (e.g., response rates, survival outcomes).Pharmacokinetic characterization of CAR-T cells (expansion/persistence).