Comparing the Efficacy of LDA, LHAA, and LA Regimens in Young Adults With Intermediate- and High-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy
A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of LDA, LHAA, and LA Regimens in Young Adults With Intermediate- and High-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究場所
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Zhejiang
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Hangzhou、Zhejiang、中国、310000
- The First Affiliated Hospital of Zhejiang University
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification;
- Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification (see Appendix Table 1);
- Age 15-65 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- Adequate hepatic and renal function: total bilirubin ≤2 mg/dL (35 μmol/L); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2× the upper limit of normal; serum creatinine ≤177 μmol/L;
- Normal cardiac function, defined as left ventricular ejection fraction (LVEF) >50%;
- Life expectancy ≥3 months;
- Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.
Exclusion Criteria:
- Acute promyelocytic leukemia;
- Central nervous system involvement by leukemia;
- History of other malignancies within the past 5 years;
- Positive for human immunodeficiency virus (HIV);
- Presence of any other serious medical condition that may limit study participation, including advanced infections, uncontrolled diabetes mellitus, severe cardiac insufficiency, or angina;
- Ineligible for intensive chemotherapy due to poor general condition;
- Pregnant or breastfeeding women;
- Inability to understand or comply with the study protocol;
- Inability to take oral medication or presence of malabsorption syndrome;
- Prior treatment with B-cell lymphoma 2 (BCL-2) inhibitors or hypomethylating agents, or current participation in any other investigational drug study;
- Inability or unwillingness to provide written informed consent.
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 |
|---|---|
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実験的：Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction therapy with lisaftoclax, daunorubicin, and cytarabine. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were classified as post-transplant or non-transplant. Post-transplant patients were randomized 1:1 to receive either lisaftoclax plus azacitidine or azacitidine alone. Non-transplant patients received lisaftoclax in combination with azacitidine. Maintenance therapy was administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity. |
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
他の名前：
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
他の名前：
Post-transplant maintenance therapy: patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy.
The combination regimen consisted of lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Azacitidine monotherapy consisted of azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Non-transplant maintenance therapy: lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
他の名前：
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実験的：Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction therapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy. All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2. |
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + homoharringtonine (2 mg/m², qd, intramuscular injection or iv infusion, D1-5) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-5) + aclarubicin (12 mg/m², maximum 20 mg, iv, D1-5).
他の名前：
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
他の名前：
Post-transplant maintenance therapy: patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy.
The combination regimen consisted of lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Azacitidine monotherapy consisted of azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Non-transplant maintenance therapy: lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
他の名前：
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実験的：Arm C:Lisaftoclax+ azacitidine
Participants received induction therapy with lisaftoclax in combination with azacitidine. Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle. Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles. For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy. All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2. |
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
他の名前：
Post-transplant maintenance therapy: patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy.
The combination regimen consisted of lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Azacitidine monotherapy consisted of azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Non-transplant maintenance therapy: lisaftoclax (400 mg, orally, D1-7) in combination with azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
他の名前：
Lisaftoclax (200 mg, orally, D1; 400 mg, orally, D2; 600 mg, orally, qd, D3-28) + azacitidine (75 mg/m², D1-7)
他の名前：
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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 |
|---|---|---|
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2-year overall survival rate (OS)
時間枠：from randomization up to 2 years
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defined as the proportion of patients who were still alive from the time of randomization for the last patient until 24 months later
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from randomization up to 2 years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
2-year event-free survival (EFS) rate
時間枠：from randomization up to 2 years after randomization
|
defined as the proportion of patients remaining free of treatment failure, hematologic relapse, MRD relapse, or death within 2 years after randomization.
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from randomization up to 2 years after randomization
|
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2-year relapse-free survival (RFS) rate
時間枠：from the date of complete remission (CR/CRi) up to 2 years after achieving response
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defined as the proportion of patients who achieved complete response (CR) or complete remission with incomplete hematologic recovery (CRi) and remained alive without disease relapse within 2 years after achieving response.
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from the date of complete remission (CR/CRi) up to 2 years after achieving response
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Safety and Tolerability
時間枠：up to 24 months
|
defined as the number of participants with adverse events and serious adverse events as assessed by NCI CTCAE v5.0
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up to 24 months
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Complete Response (CR) rate after 1/2 treatment cycles
時間枠：At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
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defined as the proportion of patients achieving complete response (CR) after the first or second cycle of induction chemotherapy.
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At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
|
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Composite Complete Response (CRc) rate after 1/2 treatment cycles
時間枠：At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
|
defined as the proportion of patients achieving CRc after the first or second cycle of induction chemotherapy.
|
At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
|
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Minimal residual disease (MRD) negativity rate after 1-2 cycles of induction chemotherapy
時間枠：At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
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defined as the the proportion of patients with negative minimal residual disease (MRD) among patients who achieve complete remission after 1-2 cycles of induction chemotherapy
|
At the end of Cycle 1 or Cycle 2 of induction chemotherapy (each cycle is 28 days)
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
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
- CN-ZY-26-02
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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
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