A Single-Arm, Prospective Study of TBI+BUMEL as Conditioning for SCT2 in Patients With Malignant Hematologic Diseases
NCT Number: NCT06548958
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Malignant Hematological Diseases
Interventions: PROCEDURE: Second Stem Cell Transplantation (SCT2)
Sponsor: The First Affiliated Hospital of Soochow University
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-10
Completion Date: 2027-06-30
Locations: Hematology Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China

Summary:
Each year, over 20,000 patients in China undergo hematopoietic stem cell transplantation (HSCT). Unfortunately, the prognosis in patients with disease relapse or graft failure was inferior. A second allogeneic hematopoietic stem cell transplantation (SCT2) has emerged as a vital salvage therapy option. Despite varying prognoses, most patients undergoing SCT2 have a five-year overall survival (OS) rate of less than 30%. The primary challenges of SCT2 include treatment strategy, immune regulation, complication management, and transplantation technique improvements. By optimizing these key aspects, SCT2 can effectively address issues that arose after the first transplant, reduce complications, and provide more effective treatment for patients.

Clinical practice indicates that SCT2 is crucial in treating various hematologic diseases. For patients who failed the first transplant (SCT1), SCT2 can more effectively treat the primary disease, provide timely hematopoietic engraftment, extend survival time, and improve the quality of life. Additionally, the successful application of SCT2 provides clinicians with more treatment options and hope. Currently, the modified BU/CY conditioning regimen, which consists of busulfan (BU) and cyclophosphamide (CY), is commonly used in SCT1 in China. However, for patients who relapse after SCT1, these drugs may become ineffective, and their physical condition often worsens, with more probability of infections and organ dysfunction. Therefore, finding new conditioning regimens is crucial.

Studies have shown that a melphalan (MEL)-based conditioning regimen may have better outcomes for patients with acute myeloid leukemia (AML) compared to a Cy-based regimen. The Conditioning regimen that includes total body irradiation (TBI) has also been considered effective for patients with acute leukemia. Thus, low-dose TBI combined with a BU + MEL regimen could be a promising conditioning regimen for SCT2. In our preliminary studies, three patients who underwent SCT2 with this regimen successfully achieved engraftment and were discharged.

Based on this, we plan to conduct a clinical study to observe the effects of the TBI+BUMEL regimen combined with SCT2 on the engraftment rate, disease relapse rate, GVHD incidence, and survival rate in patients with malignant hematologic diseases who relapsed after SCT1.

Primary Outcome Measures: The cumulative incidence of neutrophil engraftment and platelet engraftment, Neutrophil and platelet engraftment is defined as the first occurrence of 3 consecutive days with an absolute neutrophil count of at least 0.5×109/L and a platelet count of over 20×109/L for 7 consecutive days without transfusion support., on day 28±7 following SCT2|The time to reconstitution of hematopoiesis, Recovery of hemopoietic function after treatment, on day 28±7 following SCT2|The cumulative incidence of transplant-related mortality (TRM), Transplant-related mortality was defined as mortality due to any cause other than disease progression within 100 days of transplantation., within 100 days following SCT2
Secondary Outcome Measures: The cumulative incidence and grade of graft-versus-host disease (GVHD), Graft-versus-host disease (GvHD) is a medical complication following the receipt of transplanted tissue from a genetically different person., within 1 year following SCT2|The cumulative incidence of relapse, We defined relapse as any clinical evidence of progression or recurrence of original diseases., within 1 year following SCT2|Overall survival rate, We estimated OS from the time of transplant until the date of death of any cause or last follow-up for patients still alive., within 1 year following SCT2|The cumulative incidence of adverse events, Following extraction of the tumor, a blood vessel burst causing increased blood loss during the procedure, an adverse event the surgeon did not expect., within 1 year following SCT2