Thiotepa Combined With Busulfan and Fludarabine Conditioning Regimen for Haploidentical Hematopoietic Stem Cell Transplantation in Elderly Patients With High-Risk Acute Myeloid Leukemia

A Multicenter, Single-Arm, Prospective Clinical Study of Thiotepa Combined With Busulfan and Fludarabine Conditioning Regimen for Haploidentical Hematopoietic Stem Cell Transplantation in Elderly Patients With High-Risk Acute Myeloid Leukemia

Abstract:

This clinical study is designed to evaluate the efficacy and safety of a thiotepa, busulfan, and fludarabine (TBF) conditioning regimen for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly patients (≥55 years) with high-risk acute myeloid leukemia (AML). A total of 56 eligible patients will be enrolled in this prospective, single-arm, multicenter trial.

Study Design:

This is a multicenter, single-arm, prospective clinical trial. Eligible patients will receive the following conditioning regimen: thiotepa 5 mg/kg/day on Days -10 to -9; busulfan 3.2 mg/kg/day on Days -8 to -6; fludarabine 30 mg/m²/day on Days -6 to -2; and rabbit anti-thymocyte globulin (rATG) 1.5-2.5 mg/kg/day on Days -5 to -2. Hematopoietic stem cell infusion will be performed on Day 0. Graft-versus-host disease (GVHD) prophylaxis will include cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX). The primary endpoint of this study is 1-year relapse-free survival (RFS).

Inclusion Criteria:

Age 55-70 years (inclusive). Diagnosis of high-risk AML , include relapsed/refractory AML or CR MRD+ or ELN22 adverse risk group .Relapsed/refractory AML defined as at least one of the following: recurrence of leukemia cells in peripheral blood or bone marrow blasts >5% after complete remission (CR), failure to achieve remission after two courses of standard induction therapy, relapse within 12 months after consolidation therapy, relapse after 12 months that is refractory to conventional chemotherapy, multiple relapses, or persistent extramedullary leukemia）.

Scheduled to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Adequate organ function. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Written informed consent obtained.

Exclusion Criteria:

Unwillingness or refusal to accept the study treatment protocol. Presence of donor-specific anti-HLA antibodies. Known human immunodeficiency virus (HIV) infection. Active hepatitis B or C, or chronic active hepatitis. Uncontrolled active infection at the time of enrollment. Any other condition deemed by the investigator as unsuitable for study inclusion.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML); Relapsed/Refractory Acute Myeloid Leukemia (AML); High Risk Acute Myeloid Leukemia(AML)
• Intervention / Treatment: Drug: Thiotepa ;busulfan;fludarabine

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Wang MD; Phone Number: 86-8832666; Email: ywyw3172@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Yu Wang; Phone Number: 861088326001; Email: ywyw3127@sina.com
      • Principal Investigator: xiaojun huang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 55-70 years (inclusive).
2. Diagnosis of high-risk AML , include relapsed/refractory AML or CR MRD+ or ELN22 adverse risk group . Relapsed/refractory AML defined as at least one of the following: recurrence of leukemia cells in peripheral blood or bone marrow blasts >5% after complete remission (CR), failure to achieve remission after two courses of standard induction therapy, relapse within 12 months after consolidation therapy, relapse after 12 months that is refractory to conventional chemotherapy, multiple relapses, or persistent extramedullary leukemia .
3. Scheduled to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
4. Adequate organ function.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Written informed consent obtained.

Exclusion Criteria:

1. Unwillingness or refusal to accept the study treatment protocol.
2. Presence of donor-specific anti-HLA antibodies.
3. Known human immunodeficiency virus (HIV) infection.
4. Active hepatitis B or C, or chronic active hepatitis.
5. Uncontrolled active infection at the time of enrollment.
6. Any other condition deemed by the investigator as unsuitable for study 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: thiotepa 5 mg/kg/day ; busulfan 3.2 mg/kg/day ; fludarabine 30 mg/m²/day; Eligible patients will receive the following conditioning regimen: thiotepa 5 mg/kg/day on Days -10 to -9; busulfan 3.2 mg/kg/day on Days -8 to -6; fludarabine 30 mg/m²/day on Days -6 to -2; and rabbit anti-thymocyte globulin (rATG) 1.5-2.5 mg/kg/day on Days -5 to -2. Hematopoietic stem cell infusion will be performed on Day 0. Graft-versus-host disease (GVHD) prophylaxis will include cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX).

Drug: Thiotepa ;busulfan;fludarabine; Eligible patients will receive the following conditioning regimen: thiotepa 5 mg/kg/day on Days -10 to -9; busulfan 3.2 mg/kg/day on Days -8 to -6; fludarabine 30 mg/m²/day on Days -6 to -2; and rabbit anti-thymocyte globulin (rATG) 1.5-2.5 mg/kg/day on Days -5 to -2. Hematopoietic stem cell infusion will be performed on Day 0. Graft-versus-host disease (GVHD) prophylaxis will include cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year Relapse-Free Survival,（RFS）	1-year

Secondary Outcome Measures

Outcome Measure	Time Frame
1-year Overall Survival	1-year
1-year Relapse Rate	1-year
1-year Non-Relapse Mortality	1-year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 2, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 15, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Fludarabine; Busulfan; Thiotepa
• Other Study ID Numbers: 2024PHD035-001

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