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

A Single-Arm, Prospective Clinical Study of Total Body Irradiation Combined With Busulfan and Melphalan (TBI+BUMEL) as a Conditioning Regimen for Second Hematopoietic Stem Cell Transplantation in Patients With Malignant Hematologic Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Hematological Diseases
• Intervention / Treatment: Procedure: Second Stem Cell Transplantation (SCT2)

Detailed Description

The primary challenges of SCT2 include:

1. treatment strategy: eliminating residual tumor cells and addressing graft failure;
2. immune regulation: adjusting the immune system to ensure successful engraftment of new stem cells;
3. complication management: due to the poor physical condition of patients after the first transplant (SCT1), the risk of complications after SCT2 is high. This necessitates special attention to the prevention and management of post-transplant complications;
4. transplantation technique improvements: more rigorous donor screening, HLA typing, monitoring, and supportive treatment during the transplant procedure.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaojin Wu, Prof.; Phone Number: 13057493105; Email: wuxiaojin@suda.edu.cn
• Study Contact Backup: Name: Depei Wu, Prof.; Phone Number: 13951102021; Email: wudepei@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • Hematology Department, The First Affiliated Hospital of Soochow University
      • Contact: Depei Wu, Prof.; Phone Number: 13951102021; Email: wudepei@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Gender is not limited, patients between 14 to 70 years old (including critical value);
2. Malignant hematological diseases (acute/chronic myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, malignant lymphoma, etc.) diagnosed by bone marrow aspiration or biopsy according to the WHO diagnostic criteria, after the first hematopoietic stem cell transplantation, due to various reasons (including but not limited to disease relapse or graft failure) have indications for a second hematopoietic stem cell transplantation;
3. The indexes of cardiac function, liver and kidney function were within the following limits: (1) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3× Upper limit of normal (ULN); (2)Total bilirubin ≤ 3×ULN; (3) Serum creatinine ≤ 2×ULN or creatinine clearance ≥ 40mL/min; (4) Left ventricular ejection fraction (LVEF) as measured by echocardiography or multi-gated acquisition (MUGA) scan is within the normal range (> 50%);
4. Having a suitable allogeneic hematopoietic stem cell donor;
5. Expected survival ≥3 months;
6. Karnofsky (KPS) score ≥60%, Eastern Tumor Cooperative group (ECOG) status ≤ 2;
7. Patient fully understood the nature of the study, and voluntarily participates and signs informed consent.

Exclusion Criteria:

1. Patients had serious adverse reactions to investigational drugs such as allergies;
2. Patients with a history of immunodeficiency, or other acquired or congenital diseases, immunodeficiency diseases, and a history of organ transplantation;
3. Patients with hypertension, ventricular arrhythmia requiring clinical intervention, acute coronary syndrome, congestive heart failure, stroke, or other grade III or higher cardiovascular events within 6 months;
4. Received Class II or higher surgery within 4 weeks prior to enrollment;
5. Patients with active viral infections;
6. Pregnant or lactating patients;
7. The patient is currently participating in another clinical studies;
8. Patients deemed unsuitable for inclusion by other investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 40 patients with malignant hematological diseases who undergo SCT2; patients undergo SCT2 using TBI + BUMEL as a conditioning regimen

Procedure: Second Stem Cell Transplantation (SCT2); 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;; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Depei WU, Prof., The First Affiliated Hospital of Soochow University; Principal Investigator: Xiaojin Wu, Prof., The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2024
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Melphalan; Total Body Irradiation; Conditioning Regimen; Second Allogeneic Hematopoietic Stem Cell Transplantation; Malignant Hematological Diseases
• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: SOOCHOW-WXJ-2024-248

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No