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

NCT ID: NCT06673459

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2029-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TBICy

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

Group Type: EXPERIMENTAL

TBICy

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

BuCy

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Soochow University

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

Fujian Medical University Union Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: collaborator

Anhui Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Yang Xu

The First Affiliated Hospital of Soochow University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

Central Contacts

Yang Xu

Role: CONTACT

xuyang1020@126.com

86+051267781850

Facility Contacts

Yang Xu

Role: primary

xuyang1020@126.com

86+051267781850

Other Identifiers

TREAL1

Identifier Type: -

Identifier Source: org_study_id