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NCT Number: NCT06673459

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

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.

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Key information

Age range

2 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location contact

Yang Xu

CONTACT

[email protected]

86+051267781850

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • T-ALL patients aged > 2 years and ≤55 years;
  • For the first time accept allo-HSCT;
  • 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

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

Treatment and study plan

TBICy

Biological

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.

BuCy

Biological

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.

Primary outcomes

  1. Progression-free survival

    Time frame: 2 years after randomization

    estimated progression-free survival at 2 year

Secondary outcomes

  1. Overall survival

    Time frame: 2 years after randomization

    estimated overall survival at 2 year

  2. Cumulative incidence of relapse

    Time frame: 2 years after randomization

    estimated cumulative incidence of relapse at 2 year

  3. Non-relapse mortality

    Time frame: 2 years after randomization

    estimated non-relapse mortality at 2 year

  4. Adverse events

    Time frame: 2 years after randomization

    Number of participants with adverse events. Frequencies of toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) will be tabulated.

Study contacts

Contact information is provided by the study sponsor or research team.

Yang Xu

CONTACT

[email protected]

86+051267781850

Sponsors and collaborators

Lead sponsor

The First Affiliated Hospital of Soochow University

Other

Collaborators

  • Anhui Provincial Hospital
  • Children's Hospital of Soochow University
  • First Affiliated Hospital Xi'an Jiaotong University
  • Fujian Medical University Union Hospital
  • Nanfang Hospital, Southern Medical University
  • Ruijin Hospital
  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Zhejiang University

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Nov 5, 2024
Registry last updated
Nov 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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