A Single-Arm, Prospective Study of TBI+BUMEL as Conditioning for SCT2 in Patients With Malignant Hematologic Diseases

Condition(s) studied

Investigational drug(s) / intervention(s)

Second Stem Cell Transplantation (SCT2): 1. Conditioning Regimen Day -7: Semustine (Me-CCNU) 250mg/m², orally; Day -6: Total Body Irradiation (TBI) 4Gy; Day -5 to Day -4: Busulfan (Bu) 3.2mg/kg/day, administered in four divided doses, IV infusion; Day -3 to Day -2: Melphalan (Mel) 50mg/m²/day, IV infusion; 2. Donor Stem Cell Infusion (Second Hematopoietic Stem Cell Transplantation) Day 0: Intravenous infusion of donor hematopoietic stem cells (MNC ≥ 8×10⁸/kg, CD34+ cells ≥ 4×10⁶/kg).

Study 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 is often 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 the physical condition often worsens, with a higher likelihood 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 the investigators' preliminary studies, three patients who underwent SCT2 with this regimen successfully achieved engraftment and were discharged.

Based on this, the investigators 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.

Eligibility

Primary outcome measure(s)

• The cumulative incidence of neutrophil engraftment and platelet engraftment — on day 28±7 following SCT2
  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.
• The time to reconstitution of hematopoiesis — on day 28±7 following SCT2
  Recovery of hemopoietic function after treatment
• The cumulative incidence of transplant-related mortality (TRM) — within 100 days following SCT2
  Transplant-related mortality was defined as mortality due to any cause other than disease progression within 100 days of transplantation.

Trial sites (1)

More The First Affiliated Hospital of Soochow University trials in China