A Single-arm, Prospective Study of TBI + BUMEL As a Conditioning Regimen for Salvage HSCT in Patients with R/R AML

A Single-arm, Prospective Clinical Study on the Efficacy of Total Body Irradiation Combined with Busulfan and Melphalan As Conditioning Regimen for Patients with Relapsed/Refractory Acute Myeloid Leukemia Undergoing Salvage HSCT

Acute myeloid leukemia (AML) is one of the hematologic malignancies, for which patients typically undergo chemotherapy to achieve complete remission. However, approximately 30% of patients fail to respond to initial treatment, and many experience relapse after achieving remission. For patients with relapsed or refractory AML, allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option. Sibling-matched HSCT has demonstrated a disease-free survival rate of 20-30%, while unrelated donor transplants yield an overall survival rate of approximately 22%. Haploidentical transplantation is a viable alternative for patients lacking a sibling donor. A 2019 study involving 1,693 patients with relapsed/refractory (R/R) AML revealed that haploidentical transplants yielded outcomes comparable to other transplant modalities, including HLA-matched and 9/10 matched unrelated donor transplants, thus supporting haploidentical transplantation as a viable therapeutic option.

The conditioning regimen is a critical component of the transplantation. In China, the modified BU/CY conditioning regimen, which combines busulfan (BU) and cyclophosphamide (CTX), is widely utilized for tumor cytoreduction and immunosuppression. Some centers also employ post-transplant cyclophosphamide (PTCy) to mitigate the risk of graft-versus-host disease (GVHD). Despite advances, relapse remains a significant challenge. Optimizing conditioning regimens to enhance tumor cell targeting and achieve deeper remission is crucial. Additionally, many patients are unfit due to prior chemotherapy, infections, and organ dysfunction, which may make them unable to tolerate high-intensity conditioning.

Recent studies suggest that melphalan (MEL)-based conditioning regimens may offer advantages over CTX-based protocols. While total body irradiation (TBI) has been traditionally used in conditioning for HSCT, it is associated with considerable organ toxicity.

A low-dose TBI regimen combined with BU+MEL represents a promising conditioning regimen for R/R AML. In preliminary studies, 7 patients treated with this regimen successfully achieved hematopoietic stem cell engraftment. Building on these results, a clinical study is planned to evaluate further the safety and efficacy of the TBI+BUMEL (IBM) conditioning regimen in relapsed/refractory AML, with a focus on improving engraftment rates, reducing relapse rates, minimizing GVHD incidence, and enhancing overall survival outcomes.

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: Salvage Allogeneic Hematopoietic Stem Cell Transplantation

Detailed Description

The aim of this study is to observe the efficacy-related factors and adverse events of the TBI combined with BUMEL regimen as conditioning for allogeneic hematopoietic stem cell transplantation in patients with relapsed/refractory acute myeloid leukemia .

• 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
      • Contact: Xiaojin Wu, Prof.; Phone Number: 13951102021; Email: wuxiaojin@suda.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 14 and 70 years (inclusive of the age limits);

2. Patients diagnosed with relapsed/refractory (R/R) AML, meeting the World Health Organization (WHO) 2016 AML diagnostic criteria, must meet one of the following definitions:

   Relapsed AML: Leukemic cells reappear in peripheral blood or bone marrow blasts >5% after achieving complete remission (CR, CRi) (excluding other causes such as bone marrow regeneration following consolidation chemotherapy), or extramedullary leukemic infiltration occurs.

   Refractory AML:Initial cases that do not respond to two courses of standard treatment. Relapse within 12 months after consolidation therapy. Relapse after 12 months with no response to conventional chemotherapy. Two or more relapses. Persistent extramedullary leukemia.

3. Heart, liver, and kidney function must meet the following criteria:

   Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3× the upper limit of normal (ULN); Total bilirubin ≤ 3× ULN; Serum creatinine ≤ 2× ULN or creatinine clearance ≥ 40 mL/min; Left ventricular ejection fraction (LVEF), as measured by echocardiography or multi-gated acquisition (MUGA) scan, must be within the normal range (>50%).

4. Availability of a suitable allogeneic donor;
5. Life expectancy of ≥3 months;
6. Karnofsky Performance Status (KPS) ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
7. The patient understands the study protocol and voluntarily signs the informed consent form.

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. Patients received Class II or higher surgery within 4 weeks prior to enrollment;
5. Patient has an active and difficult-to-control infection, including but not limited to active fungal, bacterial, or viral infections that require systemic treatment, such as active HIV, hepatitis B or C;
6. Patient has active central nervous system leukemia infiltration;
7. Pregnant or lactating patients;
8. Patient is currently participating in another clinical studies;
9. Other conditions where the investigator deems the patient unsuitable for inclusion.

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 relapsed/refractory acute myeloid leukemia who undergo HSCT; patients undergo HSCT using TBI + BUMEL as a conditioning regimen

Procedure: Salvage Allogeneic Hematopoietic Stem Cell Transplantation; TBI+BUMEL (IBM) Conditioning Regimen Day -7: Semustine (Me-CCNU) 250mg/m², orally, Day -7; Day -6: Total Body Irradiation (TBI) 4Gy, in two parts, Day -6; 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 (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 HSCT
The time to reconstitution of hematopoiesis	recovery of hemopoietic function after treatment	on day 28±7 following HSCT
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 HSCT

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 HSCT
The cumulative incidence of relapse	We defined relapse as any clinical evidence of progression or recurrence of original diseases.	within 1 year following HSCT
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 HSCT
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 HSCT

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Xiaojin Wu, Prof., the First Affiliated Hospital of Soochow University; Study Chair: Depei Wu, Prof., the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Melphalan; Total Body Irradiation; Conditioning Regimen; Relapsed or Refractory Acute Myeloid Leukemia; Salvage Allogeneic Hematopoietic Stem Cell Transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: SOOCHOW-WXJ-2024-475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No