Lisaftoclax Plus Azacitidine Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse
Maintenance Therapy With Lisaftoclax Plus Azacitidine After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse: A Multicenter, Open-Label, Randomized Controlled Trial
This study evaluates the efficacy and safety of maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with acute myeloid leukemia (AML) at high risk of relapse.
The main questions this study aims to answer are:
- Does maintenance therapy with lisaftoclax plus azacitidine improve disease-free survival compared with observation alone after allo-HSCT?
- Does maintenance therapy reduce relapse and improve overall survival?
- What adverse events and safety outcomes are associated with this treatment strategy?
Researchers will compare maintenance therapy with lisaftoclax plus azacitidine with observation or best supportive care in patients with AML at high risk of relapse following allo-HSCT.
Participants will:
- Be randomly assigned in a 2:1 ratio to receive either maintenance therapy with lisaftoclax plus azacitidine or observation.
- Receive study treatment for up to 12 cycles or undergo observation according to the study assignment.
- Undergo regular follow-up assessments, disease monitoring, and safety evaluations after transplantation.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 3
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment in this study:
- Diagnosed with acute myeloid leukemia (AML), excluding acute promyelocytic leukemia, according to the WHO 2022 classification, and without FLT3-ITD or FLT3-TKD mutations.
- Presence of at least one of the following high-risk features:
1) Adverse-risk AML according to the ELN 2022 risk classification; 2) Refractory AML; 3) Relapsed AML; 4) Persistent measurable residual disease positivity prior to transplantation; 5) Secondary AML transformed from myelodysplastic syndrome or myeloproliferative neoplasm.
3. Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT).
4. Stable hematologic recovery, defined as: Absolute neutrophil count ≥ 1.0 × 10⁹/L without G-CSF support; and Platelet count ≥ 50 × 10⁹/L without platelet transfusion within 7 days prior to randomization.
5. Age ≥18 years and ≤75 years. 6. Eastern Cooperative Oncology Group performance status of 0-2. 7. Ability to provide written informed consent before initiation of any study procedures.
8. Written informed consent may be provided by the participant or an authorized immediate family member in accordance with local regulations.
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded from the study:
- Evidence of disease relapse or impending relapse prior to randomization after transplantation, as determined by morphologic assessment or flow cytometry.
- Active or uncontrolled acute graft-versus-host disease (aGVHD) requiring systemic immunosuppressive therapy.
- Uncontrolled active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 7 days prior to enrollment.
- Moderate or severe hepatic impairment, as defined by the Child-Pugh classification.
- Severe renal impairment, defined as creatinine clearance <30 mL/min (calculated using the Cockcroft-Gault formula) or requirement for dialysis.
- Pregnancy, or unwillingness/inability to use adequate contraception during the study treatment period.
- Psychiatric disorders or other medical conditions that, in the investigator's judgment, would interfere with compliance with study treatment, monitoring, or study procedures.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
介入なし：観察
|
|
|
実験的：Lisaftoclax plus Azacitidine Maintenance Therapy
|
Participants will receive maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Lisaftoclax will be administered orally at a dose of 400 mg once daily on Days 1-7 of each treatment cycle.
Azacitidine will be administered at a dose of 32 mg/m² by subcutaneous injection or intravenous infusion on Days 1-5 of each treatment cycle.
Each treatment cycle is 28 days in length.
Maintenance therapy will be administered for up to 12 cycles or until 15 months after allo-HSCT, whichever occurs first.
The dose of lisaftoclax may be modified according to concomitant medications and treatment-related hematologic toxicities.
The interval between treatment cycles may be extended based on individual tolerability and hematologic recovery.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Disease-Free Survival
時間枠：2 years
|
Disease status (including relapse) and survival outcomes will be evaluated for the assessment of disease-free survival (DFS).
DFS is defined as the time from randomization to the first occurrence of relapse or death from any cause.
Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status (MRD-positive vs. MRD-negative) to assess the consistency of treatment effects across MRD subgroups.
|
2 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Cumulative Incidence of Relapse
時間枠：2 years
|
The cumulative incidence of relapse will be assessed during the follow-up period.
|
2 years
|
|
Overall Survival
時間枠：2 years.
|
Overall survival (OS) is defined as the time from randomization to death from any cause.
Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status to assess the consistency of treatment effects between MRD-positive and MRD-negative patients.
|
2 years.
|
|
Cumulative Incidence of Pre-emptive Therapy.
時間枠：2 years
|
Pre-emptive therapy rate is defined as the proportion of patients who receive additional anti-leukemic treatment triggered by measurable residual disease positivity or other molecular evidence of impending relapse after allogeneic hematopoietic stem cell transplantation.
|
2 years
|
|
Cumulative Incidence of Non-Relapse Mortality
時間枠：2-years.
|
Non-relapse mortality, defined as death without prior disease relapse or progression, assessed as a cumulative incidence.
|
2-years.
|
|
Treatment-Related Adverse Events
時間枠：From initiation of maintenance therapy to 30 days after last dose of study drug.
|
Incidence, severity, and type of adverse events will be evaluated and graded according to CTCAE v5.0 during maintenance therapy and follow-up.
|
From initiation of maintenance therapy to 30 days after last dose of study drug.
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IIT2026015
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。