A Single-arm, Prospective Study of a Clad-LABU Conditioning Regimen in HSCT for R/R MDS/AML in Elderly Patients

Summary

Acute myeloid leukemia (AML) is one of the most common hematologic malignancies. With increasing life expectancy and the aging of society, the incidence of AML in the elderly population is rising. The prognosis of elderly AML patients is significantly worse than that of younger patients: the 5-year overall survival rate in patients over 60 years is less than 20%, while the median survival in patients over 80 years is only 3-6 months . Improving the overall prognosis of elderly AML has become a hot topic in current hematology research.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach that involves intravenous infusion of hematopoietic stem cells with the goal of restoring bone marrow and immune function. Although several studies have focused on allo-HSCT in elderly patients, factors affecting transplant outcomes remain controversial, influencing clinical decision-making. Julian et al. retrospectively analyzed 103 elderly patients with relapsed/refractory AML who underwent allogeneic transplantation, showing that high-dose melphalan sequential chemotherapy was effective and well tolerated in elderly AML patients, with a 3-year overall survival rate exceeding 40%; disease prognosis was closely related to donor source and pre-transplant leukemic burden . Furthermore, studies on haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly patients are limited. A retrospective analysis from Peking University People's Hospital involving 199 elderly AML patients (≥50 years) who underwent allo-HSCT confirmed that haplo-HSCT is feasible in elderly AML patients; however, transplantation in a refractory/active disease state was associated with poorer transplant outcomes. A study from the EBMT summarized outcomes in 360 elderly patients (≥70 years) who underwent allogeneic transplantation in a non-remission state, reporting 2-year overall survival rates of 25.9%, 43%, and 62.4% for haplo-HSCT, unrelated donor, and matched sibling donor transplants, respectively.

The challenge in treating relapsed/refractory elderly AML patients lies in improving the tolerability of conditioning regimens and reducing conditioning-related toxicity, thereby increasing the success rate of transplantation. Venetoclax (VEN), an orally administered selective small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, has demonstrated efficacy in randomized clinical trials across several hematologic malignancies. As monotherapy for relapsed/refractory AML, VEN shows modest efficacy while exhibiting good tolerability . In the global phase III clinical trial of venetoclax, in newly diagnosed AML patients unfit for intensive induction chemotherapy, venetoclax combined with azacitidine demonstrated significantly superior clinical efficacy compared to azacitidine alone, with a response rate (CR+CRi) more than three times higher than that of the control group, enabling patients to achieve faster and deeper remissions. Our center has also accumulated extensive experience with venetoclax in post-transplant maintenance therapy for AML and in the treatment of relapsed/refractory AML. Additionally, studies have confirmed the safety and efficacy of high-dose venetoclax in newly diagnosed AML . Based on the aforementioned clinical efficacy and theoretical rationale, our center previously conducted a study investigating the venetoclax + azacitidine + busulfan (VABu) regimen in allogeneic HSCT for elderly AML patients, confirming that this novel regimen reduces conditioning-related chemotherapy toxicity, improves tolerability, and demonstrates advantages in decreasing cardiotoxicity, mucositis, infections, and organ dysfunction. Lisaftolax, as a second-generation BCL-2 inhibitor, can partially overcome venetoclax resistance and improve patient outcomes.

Nevertheless, a consensus on the comprehensive systemic treatment strategy for elderly AML patients has not yet been reached globally. For high-risk or relapsed/refractory elderly AML patients, after risk stratification and assessment of response to chemotherapy, those who are suitable for allo-HSCT may receive a conditioning regimen consisting of cladribine bridged to lisaftolax and busulfan (Clad/LABu), aiming to achieve longer remission duration, reduce post-transplant relapse rates, and improve long-term survival in elderly AML patients.

Conditions

• Relapsed or Refractory Acute Myeloid Leukemia (AML)
• MDS (Myelodysplastic Syndrome)

Interventions

PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Clad+LABU Conditioning Regimen :Cladribine: 6.0 mg/m² once daily for 3 days, intravenous infusion on days -14 to -12;Cytarabine (Ara-C): 1.0 g/m² once daily for 3 days, intravenous infusion on days -14 to -12;Lomustine (CCNU): 250 mg/m² once on day -11, orally;Lisaftoclax: 1200 mg once daily for 6 days, orally on days -11 to -6;Azacitidine (AZA): 75 mg/m² once daily for 5 days, subcutaneous injection on days -10 to -6. Alternatively, or Decitabine (DAC): 20 mg/m² once daily for 5 days, intravenous infusion on days -10 to -6;Busulfan: 0.8 mg/kg every 6 hours for 3 days, intravenous infusion on days -5 to -3.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University

  lead OTHER

Principal Investigators

• Depei Wu · The First Affiliated Hospital of Soochow University

• Xiaojin Wu · The First Affiliated Hospital of Soochow University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2029-03-30

Completion

2029-06-30

Countries

• China

Study Locations