AML (Acute Myelogenous Leukemia, HSCT
Conditions
Brief summary
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.
Interventions
DRUGSonrotoclax, cladribine, and standard-dose cytarabine
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.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 1.Patients with a confirmed diagnosis of relapsed or refractory acute myeloid leukemia (AML) based on bone marrow morphology, immunophenotyping, and cytogenetics. * 2\. Patients who are planned to undergo allogeneic hematopoietic stem cell transplantation, including HLA-matched or HLA-mismatched related allogeneic transplantation, as well as unrelated donor transplantation. * 3\. Age between 18 and 65 years, inclusive, regardless of gender. * 4\. Eastern Cooperative Oncology Group performance status (ECOG) of 0-2. * 5\. Written informed consent must be obtained prior to the initiation of any study-related procedures. For patients aged 18 years or older, the consent form may be signed by the patient or by a direct relative. Should the patient's own signature be judged to be potentially harmful to their clinical care, consent may instead be given by a legal guardian or a direct relative.
Exclusion criteria
* 1\. Uncontrolled active infection (bacterial, fungal, or viral). * 2\. Known positive serology for human immunodeficiency virus (HIV) or active hepatitis C virus (HCV). * 3\. Psychiatric disorders or other medical conditions that preclude compliance with the study treatment and monitoring requirements. * 4\. Pregnant patients, or patients who are unwilling or unable to use adequate contraceptive measures during the treatment period. * 5\. Prior hematopoietic stem cell transplantation. * 6\. Active cardiac disease, defined as one or more of the following: History of uncontrolled or symptomatic angina pectoris; Myocardial infarction within 6 months prior to study enrollment; History of arrhythmia requiring medication or clinically significant symptomatic arrhythmia; Uncontrolled or symptomatic congestive heart failure (\> New York Heart Association \[NYHA\] class 2); Ejection fraction below the lower limit of normal; Previous coronary angioplasty or stent implantation. * 7\. Severe hepatic impairment, defined as liver function parameters (ALT, TBIL) \> 3 × upper limit of normal (ULN); or severe renal impairment, defined as serum creatinine (Cr) \> 2 × ULN, or 24-hour urine creatinine clearance \< 50 mL/min; or any other condition that, in the investigator's opinion, renders the patient unsuitable for treatment with the study drug. * 8\. Any other condition that, in the investigator's opinion, makes the patient ineligible for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| One year overall survival (OS) rate after treatment. | One year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of graft-versus-host disease (GVHD) | 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>) | one year after treatment | — |
| Treatment-related adverse events as assessed by CTCAE v4.0 | one year after treatment | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
| Response rate (complete remission [CR] and complete remission with incomplete hematologic recovery [CRi]) after salvage chemotherapy | one month after chemotherapy | — |
| 1-year relapse-free survival (RFS) rate | one year after treatment | — |
| 1-year cumulative incidence of relapse (CIR) | one year after treatment | — |
| 1-year treatment-related mortality (TRM) rate | one year after treatment | — |
| Assessment of hematopoietic reconstitution post-transplantation | One year after HSCT | 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. |
| Rate of bridging to allogeneic hematopoietic stem cell transplantation | one year after treatment | — |
Outcome results
None listed