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

A Single-arm, Prospective Study of a Cladribine-Bridged Lisaftolax and Busulfan Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Myelodysplastic Syndromes and Acute Myeloid Leukemia in Elderly Patients

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.

Study Overview

• Status: Recruiting
• Conditions: MDS (Myelodysplastic Syndrome); Relapsed or Refractory Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Detailed Description

The aim of this study is to observe the efficacy-related factors and adverse events of the Clad-LABU regimen as conditioning for allogeneic hematopoietic stem cell transplantation in patients with relapsed/refractory MDS/AML in Elderly Patients

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaojin Wu; Phone Number: +8613057493105; Email: wuxiaojin@suda.edu.cn
• Study Contact Backup: Name: Depei Wu; Phone Number: +8613951102021; Email: wudepei@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • the First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 50years.
• Meet the 2022 World Health Organization (WHO) diagnostic criteria for acute myeloid leukemia (AML),MDS, and be diagnosed with relapsed/refractory AML after treatment, fulfilling any of the following definitions:
• Relapsed AML: Reappearance of leukemic cells in peripheral blood, bone marrow blasts >5% (excluding other causes such as bone marrow regeneration after consolidation chemotherapy), or extramedullary infiltration of leukemic cells after achieving complete remission (CR or CRi).
• Refractory AML: Newly diagnosed cases that failed to respond after 2 courses of standard therapy; patients who relapsed within 12 months after consolidation therapy following CR; patients who relapsed after 12 months but failed to respond to conventional chemotherapy; patients with 2 or more relapses; persistent extramedullary leukemia.
• MDS:Myelodysplastic Neoplasms (MDS)MDS are a group of clonal hematopoietic stem cell disorders characterized by: Dysplastic hematopoiesis (abnormal development of blood cells in the bone marrow); Cytopenias (one or more lineages of blood cells are reduced in number); Increased risk of transformation to acute myeloid leukemia (AML).Key diagnostic criteria (per WHO 2022 classification): Persistent cytopenia(s) for ≥4 months (unless specific genetic abnormalities are present); Morphological dysplasia in ≥10% of cells in one or more lineages; Presence of MDS-defining genetic abnormalities (e.g., SF3B1 mutation, isolated del(5q), TP53 biallelic alteration).
• Cardiac, hepatic, and renal function test results within the following limits:

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN);Total bilirubin ≤ 3 × ULN;Serum creatinine ≤ 2 × ULN or creatinine clearance ≥ 40 mL/min;Left ventricular ejection fraction (LVEF) measured by echocardiography or multigated acquisition (MUGA) scan within the normal range (>50%).

• Have a suitable allogeneic donor.
• Expected survival ≥ 1 month.
• Karnofsky Performance Status (KPS) ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
• The patient understands the study protocol and voluntarily signs the informed consent form.

Exclusion Criteria:

• Patients had serious adverse reactions to investigational drugs such as allergies;
• Patients with a history of immunodeficiency, or other acquired or congenital diseases, immunodeficiency diseases, and a history of organ transplantation;
• Patients with hypertension, ventricular arrhythmia requiring clinical intervention, acute coronary syndrome, congestive heart failure, stroke, or other grade III or higher cardiovascular events within 6 months;
• Patients received Class II or higher surgery within 4 weeks prior to enrollment;
• Patient has an active and difficult-to-control infection, including but not limited to active fungal, bacterial, or viral infections that require systemic treatment, such as active HIV, hepatitis B or C;
• Patient has active central nervous system leukemia infiltration;
• Pregnant or lactating patients;
• Patient is currently participating in another clinical studies;
• Other conditions where the investigator deems the patient unsuitable for 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: 30 patients with relapsed/refractory MDS/AML who undergo HSCT; patients undergo HSCT using Clad-LABu as a conditioning regimen

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	We estimated OS from the time of transplant until the date of death of any cause or last follow-up for patients still alive.	within 1 year following HSCT
Relapse free survival rate	Relapse-Free Survival (RFS) is defined as the time from transplantation until disease relapse or death from any cause, whichever occurs first.	within 1 year following HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cumulative incidence of transplant-related mortality (TRM)	Transplant-related mortality was defined as mortality due to any cause other than disease progression within 100 days of transplantation.	within 100 days following HSCT
The cumulative incidence and grade of graft-versus-host disease (GVHD)	Graft-versus-host disease (GVHD) is a medical complication following the receipt of transplanted tissue from a genetically different person.	within 1 year following HSCT
The cumulative incidence of relapse	We defined relapse as any clinical evidence of progression or recurrence of original diseases.	within 1 year following HSCT
The cumulative incidence of neutrophil engraftment and platelet engraftment	Neutrophil and platelet engraftment is defined as the first occurrence of 3 consecutive days with an absolute neutrophil count of at least 0.5×109/L and a platelet count of over 20×109/L for 7 consecutive days without transfusion support.	on day 28±7 following HSCT]

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Depei Wu, the First Affiliated Hospital of Soochow University; Study Chair: Xiaojin Wu, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Busulfan; Cladribine; Allogeneic Hematopoietic Stem Cell Transplantation; Conditioning Regimen; Relapsed or Refractory Acute Myeloid Leukemia; Lisaftolax
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Anemia; Leukemia; Myelodysplastic Syndromes; Anemia, Refractory; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts
• Other Study ID Numbers: SOOCHOW-WXJ-2025-1293

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No