Clad-LABU conditioning before allogeneic stem cell transplant for relapsed or refractory AML/MDS in older adults

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

This will try a Clad-LABU chemotherapy conditioning plan before allogeneic stem cell transplant in people aged 50 and older with relapsed or refractory AML or MDS.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07500753 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm study testing a Clad-LABU conditioning regimen given before allogeneic hematopoietic stem cell transplantation in elderly patients with relapsed or refractory AML or MDS. Eligible participants are adults aged 50 years or older who meet relapsed or refractory disease criteria and are candidates for allo-HSCT. The study will collect data on transplant outcomes, factors linked to efficacy, and treatment-related adverse events following the conditioning and transplant. All treatment and follow-up are performed at The First Affiliated Hospital of Soochow University.

Who should consider this trial

Good fit: Ideal candidates are people aged 50 or older with relapsed or refractory AML or MDS who are medically eligible to receive allogeneic hematopoietic stem cell transplantation.

Not a fit: Patients who are too frail for transplant, have uncontrolled infections or severe comorbidities, or who do not meet the relapsed/refractory disease criteria are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the regimen could increase the chance of durable remission and improve survival after transplant for older patients with relapsed or refractory AML or MDS.

How similar studies have performed: Previous work with reduced-intensity and cladribine-containing conditioning regimens has shown some promise in older patients, but the specific Clad-LABU combination used here is relatively novel and not widely tested in this population.

Eligibility criteria

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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Xiaojin Wu

Conditions Relapsed or Refractory Acute Myeloid Leukemia; MDS; Conditioning Regimen; Cladribine; Lisaftolax; Busulfan; Allogeneic Hematopoietic Stem Cell Transplantation