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

NCT06673459 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: TREAL1
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

T-Cell Lymphocytic Leukemia; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; Total Body Irradiation; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  estimated progression-free survival at 2 year

  2 years after randomization

Secondary Outcomes (4)

• Overall survival

  2 years after randomization

• Cumulative incidence of relapse

  2 years after randomization

• Non-relapse mortality

  2 years after randomization

• Adverse events

  2 years after randomization

Study Arms (2)

TBICy

EXPERIMENTAL

Patients enrolled in this arm will receive total body irradiation plus cyclophosphamide as conditioning regimen.

Biological: TBICy

BuCy

ACTIVE COMPARATOR

Patients enrolled in this arm will receive busulfan plus cyclophosphamide as conditioning regimen.

Biological: BuCy

Interventions

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.

TBICy

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.

BuCy

Eligibility Criteria

• Age: 2 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

MeSH Terms

Conditions

Leukemia, T-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Yang Xu

CONTACT

86+051267781850; xuyang1020@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The First Affiliated Hospital of Soochow University

Study Record Dates

• First Submitted: November 2, 2024
• First Posted: November 5, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: November 5, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)