A Prospective Phase II Clinical Trial of Salvage Chemotherapy With Sonrotoclax, Cladribine, and Standard-dose Cytarabine, Sequentially Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Enrollment
- 50
- Primary Endpoint
- One year overall survival (OS) rate after treatment.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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-
- •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.
Arms & Interventions
salvage treatment
Salvage chemotherapy with Sonrotoclax, cladribine, and standard-dose cytarabine in patients with relapsed/refractory acute myeloid leukemia.
Intervention: Sonrotoclax, cladribine, and standard-dose cytarabine (Drug)
Outcomes
Primary Outcomes
One year overall survival (OS) rate after treatment.
Time Frame: One year
Secondary Outcomes
- 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)
- Rate of bridging to allogeneic hematopoietic stem cell transplantation(one year after treatment)
- Assessment of hematopoietic reconstitution post-transplantation(One year after HSCT)
- 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)