The goal of this clinical trial is to treat adult patients with relapsed/refractory acute myeloid leukemia (AML) using a salvage chemotherapy regimen consisting of Sonrotoclax, cladribine, and standard-dose cytarabine, sequentially followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The main questions it aims to answer are: Does this treatment regimen improve the 2-year overall survival (OS) rate, relapse-free survival (RFS) rate, and cumulative incidence of relapse (CIR) in this patient population? What is the safety profile of this combination and sequential transplant strategy, particularly regarding treatment-related mortality (TRM) and adverse events? As this is a single-arm phase II study, there is no comparator group. Participants will: Receive salvage chemotherapy with cladribine (5 mg/m² on days 1-5), cytarabine (100 mg/m² twice daily on days 1-5), and Sonrotoclax (escalating doses from 40 mg to 320 mg on days 1-14). Undergo allogeneic hematopoietic stem cell transplantation as a bridge therapy within 1 to 4 weeks after completing chemotherapy. Potentially receive Sonrotoclax as maintenance therapy after hematopoietic reconstitution post-transplant, at the investigator's discretion. Undergo regular follow-up visits for clinical assessments, disease monitoring, and survival evaluation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
After enrollment, patients will receive salvage chemotherapy with Sonrotoclax, cladribine, and standard-dose cytarabine, and will be bridged to allogeneic hematopoietic stem cell transplantation within 1 to 4 weeks after completion of chemotherapy. Following hematopoietic reconstitution post-transplantation, Sonrotoclax may be administered as maintenance therapy at the investigator's discretion.
One year overall survival (OS) rate after treatment.
Time frame: One year
Response rate (complete remission [CR] and complete remission with incomplete hematologic recovery [CRi]) after salvage chemotherapy
Time frame: one month after chemotherapy
1-year relapse-free survival (RFS) rate
Time frame: one year after treatment
1-year cumulative incidence of relapse (CIR)
Time frame: one year after treatment
1-year treatment-related mortality (TRM) rate
Time frame: one year after treatment
Rate of bridging to allogeneic hematopoietic stem cell transplantation
Time frame: one year after treatment
Assessment of hematopoietic reconstitution post-transplantation
Hematopoietic reconstitution refers to Neutrophil engraftment and platelet engraftment. Neutrophil engraftment was defined as the first of three consecutive days with an absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L. Platelet engraftment was defined as a platelet count ≥ 20 × 10⁹/L for seven consecutive days without platelet transfusion support.
Time frame: One year after HSCT
Incidence and severity of graft-versus-host disease (GVHD)
Time frame: One year
Rates of MRD-negative complete remission (CR<sub>MRD-</sub>) and MRD-negative complete remission with incomplete hematologic recovery (CRi<sub>MRD-</sub>)
Time frame: one year after treatment
Treatment-related adverse events as assessed by CTCAE v4.0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: one year after treatment
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