BuCy Vs. TBICy for Allo-HSCT in T-ALL Patients

Busulfan Plus Cyclophosphamide Vs. Total Body Irradiation Plus Cyclophosphamide for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute T Lymphoblastic Leukemia: a Randomized Controlled, Open-label, Multi-center Clinical Trial

T-cell acute lymphoblastic leukemia (T-ALL), a hematological malignant neoplasm of immature T cells, accounting for a morbidity of 10-15% among pediatric and 20-25% among adult patients of ALL. Despite the application of improved intensive therapies, the overall survival (OS) of T-ALL patients is still unsatisfactory, with a 5-year OS rate of less than 60% in adults and 85% in children. Over the past few decades, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has emerged as a potential and the most likely curative treatment for patients with high-risk hematological malignant neoplasms, and it has been proven that allo-HSCT could hold the potential to improve the prognosis of T-ALL patients and may even cure T-ALL.

The two most common myeloablative conditioning regimens for T-ALL patients with allo-HSCT were total body irradiation (TBI) plus cyclophosphamide (TBI-Cy) and busulfan (Bu) plus cyclophosphamide (BuCy). The most common use conditioning regimen for ALL patients is the TBI-Cy conditioning regimen over other hematological malignancy patients because TBI possess potent and distinct anti-leukemic effects, particularly in organs not easily affected by systemic chemotherapy and intense immunosuppressive effects. However, TBI-based conditioning regimens may cause a high risk of cataracts, interstitial pneumonitis (IP), engraftment failure and even subsequent malignant neoplasms (SMNs). To avoid these disadvantages, intravenous Bu replaced TBI as a part of conditioning.

Extensive studies have shown that allo-HSCT with conditioning regimens based on TBI could benefit survival compared with conditioning regimens based on chemotheraphy in treating ALL. We retrospectively analyzed post-10-year data from T-ALL patients from two transplant centers, and all the databases were used to eliminate confounding factors via PSM. We demonstrated that the TBI-Cy conditioning regimen had inferior efficacy to the BuCy conditioning regimen, especially for T-ALL patients who were children, refractory, had extramedullary disease before transplantation, had active disease or an MRD-positive status at allo-HSCT, or who received haplo-HSCT.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; T-Cell Lymphocytic Leukemia; Total Body Irradiation
• Intervention / Treatment: Biological: TBICy; Biological: BuCy

• Study Type: Interventional
• Enrollment (Estimated): 430
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yang Xu; Phone Number: 86+051267781850; Email: xuyang1020@126.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University
      • Contact: Yang Xu; Phone Number: 86+051267781850; Email: xuyang1020@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. T-ALL patients aged > 2 years and ≤55 years;
2. For the first time accept allo-HSCT;
3. With Eastern Cooperative Oncology Group (ECOG) performance status of 0-3; 4. Signing an informed consent form, having the ability to comply with study and follow-up procedures.

Exclusion Criteria:

1. With other malignancies;
2. With a previous history of autologous hematopoietic cell transplantation, allogeneic hematopoietic cell transplantation or chimeric antigen receptor T cell therapy;
3. With uncontrolled infection intolerant to haploidentical hematopoietic cell transplantation;
4. With severe organ dysfunction;
5. In pregnancy or lactation period;
6. With any conditions not suitable for the trial (investigators' decision).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TBICy; Patients enrolled in this arm will receive total body irradiation plus cyclophosphamide as conditioning regimen.	Biological: TBICy; The TBI-Cy group was administered 250 mg/m2/d oral Me-CCNU on day -8. A total of 12 Gy TBI was for each patient and fractionated dose was 2 Gy twice daily or 4Gy once daily on days -8 to -6. Occluding of the lung fields during TBI, the corresponding irradiation dose reduced to a total of 8 Gy. On day -5, the schedule was intravenous 2 g/m2 Ara-C every 12 hours. Then intravenous 1.8 g/m2 CTX once per day from days -4 to -3.
Active Comparator: BuCy; Patients enrolled in this arm will receive busulfan plus cyclophosphamide as conditioning regimen.	Biological: BuCy; The BuCy group received oral Me-CCNU 250 mg/m2/d twice daily on day -8, intravenous cytosine arabinoside (Ara-C) 2 g/m2 twice daily on day -7, intravenous Bu 3.2 mg/kg/d from days -6 to -4, and intravenous cyclophosphamide (CTX) 1.8 g/m2/d from days -3 to -2. There were no patients accepted oral Bu.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	estimated progression-free survival at 2 year	2 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	estimated overall survival at 2 year	2 years after randomization
Cumulative incidence of relapse	estimated cumulative incidence of relapse at 2 year	2 years after randomization
Non-relapse mortality	estimated non-relapse mortality at 2 year	2 years after randomization
Adverse events	Number of participants with adverse events. Frequencies of toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) will be tabulated.	2 years after randomization

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: First Affiliated Hospital Xi'an Jiaotong University; Ruijin Hospital; Wuhan Union Hospital, China; Fujian Medical University Union Hospital; Zhejiang University; Children's Hospital of Soochow University; Anhui Provincial Hospital; Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: November 2, 2024
• First Submitted That Met QC Criteria: November 2, 2024
• First Posted (Estimated): November 5, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell
• Other Study ID Numbers: TREAL1

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