Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML
A Phase Ib Study of Liposomal Mitoxantrone Combined With Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit Patients With Acute Myeloid Leukemia
This prospective, open-label, multicenter phase Ib trial will evaluate the safety, tolerability, and RP2D of the VAM regimen (liposomal mitoxantrone + azacitidine [AZA] + venetoclax [VEN]) in elderly or unfit patients with newly diagnosed AML. A standard 3+3 dose escalation will enroll 12-30 patients, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed.
Induction therapy will consist of up to two 28-day cycles. Responders achieving CR/CRi/MLFS will be eligible for up to 4 consolidation cycles (total ≤6 cycles), after which they will proceed to maintenance with either AZA+VEN or observation.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 1
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:
Subjects eligible for enrollment in this study must meet all of the following criteria:
- Diagnosis of acute myeloid leukemia (AML) according to the WHO 2022 or ICC criteria, excluding acute promyelocytic leukemia (APL).
- No prior therapy for AML, except hydroxyurea for the management of hyperleukocytosis.
Meeting at least one of the following criteria:
- Age ≥ 75 years;
- Age 18-74 years with at least one of the following conditions precluding suitability for intensive chemotherapy:
i. ECOG performance status 2-3; ii. Cardiac dysfunction with left ventricular ejection fraction (LVEF) ≤ 50%; iii. Pulmonary dysfunction with diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; iv. Creatinine clearance 30-45 mL/min; v. Other major organ dysfunction or comorbidities that, in the investigator's judgment, render the patient unsuitable for intensive chemotherapy.
- ECOG performance status 0-3.
- Life expectancy ≥ 3 months.
- Patients of childbearing potential agree to use effective contraception during the treatment period and for at least 6 months after the last dose of study treatment.
- Voluntary written informed consent provided.
Exclusion Criteria:
Subjects who meet any of the following criteria will not be eligible for enrollment in this study:
- Acute promyelocytic leukemia (APL)..
- Active central nervous system (CNS) leukemia.
- Prior targeted therapy or chemotherapy for AML, excluding hydroxyurea.
- Uncontrolled active infection.
- Uncontrolled cardiovascular disease: New York Heart Association (NYHA) class III-IV heart failure, myocardial infarction or unstable angina within 6 months before enrollment, or uncontrolled hypertension.
- Left ventricular ejection fraction (LVEF) < 40%.
- Concurrent active malignancy, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer.
- Known hypersensitivity to the study drugs or their excipients.
- Pregnant or breastfeeding women.
- Any other condition that, in the investigator's judgment, would make the patient unsuitable for study participation.
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
|
実験的：Venetoclax, azacitidine combined with liposome mitoxantrone as induction regimen
The trial will employ a standard 3+3 dose escalation design, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed. Venetoclax duration will be sequentially escalated (9 vs. 14 days), choosing the longest duration without dose-limiting toxicity (DLT) in 3-6 evaluable patients. The RP2D for liposomal mitoxantrone is the highest dose with ≤1 DLT in 6 patients; if DL4 is tolerated, RP2D = 20 mg/m² on day 1. |
Liposome Mitoxantrone: 8, 12, 16, and 20 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks
Venetoclax(9 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po), every 4 weeks Venetoclax(14 days): 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7, every 4 weeks
|
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 |
|---|---|---|
|
Dose-Limiting Toxicity (DLT)
時間枠：Cycle 1(up to 42 days)
|
To evaluate the safety, tolerability, and RP2D of the VAM regimen in newly diagnosed elderly/unfit AML patients.
|
Cycle 1(up to 42 days)
|
|
Incidence of treatment-related adverse events
時間枠：From day 1 of treatment to 28 days after the last dose
|
The safety of the drug was evaluated by NCI-CTC AE 5.0 standard which including hematologic and non-hematologic toxicity
|
From day 1 of treatment to 28 days after the last dose
|
|
Composite complete remission (CRc) rate
時間枠：Up to approximately eight weeks
|
Proportion of patients with complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia-free state (MLFS)
|
Up to approximately eight weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Complete remission (CR) rate
時間枠：Up to approximately eight weeks
|
Proportion of patients with complete remission (CR)
|
Up to approximately eight weeks
|
|
Complete remission with incomplete hematologic recovery (CRi) rate
時間枠：Up to approximately eight weeks
|
Proportion of patients with complete remission with incomplete hematologic recovery (CRi)
|
Up to approximately eight weeks
|
|
Morphologic leukemia-free state (MLFS) rate
時間枠：Up to approximately eight weeks
|
Proportion of patients with morphologic leukemia-free state (MLFS)
|
Up to approximately eight weeks
|
|
Event-free survival (EFS)
時間枠：Up to approximately 5 years
|
It is defined as the time from the start of study treatment to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first)
|
Up to approximately 5 years
|
|
Overall survival (OS)
時間枠：Up to approximately 5 years
|
It is defined as the time from the start of study treatment to the death from any cause
|
Up to approximately 5 years
|
|
Relapse-free Survival (RFS)
時間枠：Up to approximately 5 years
|
It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up
|
Up to approximately 5 years
|
|
Duration of Response (DoR)
時間枠：Up to approximately 5 years
|
It is defined as the time from the first documentation of CRc to relapse
|
Up to approximately 5 years
|
|
30-day postinduction mortality
時間枠：Up to approximately 30 days
|
It is defined as death from any cause within 30 days after the start of induction
|
Up to approximately 30 days
|
|
60-day postinduction mortality
時間枠：Up to approximately 60 days
|
t is defined as death from any cause within 60 days after the start of induction
|
Up to approximately 60 days
|
|
Measurable Residual Disease (MRD) negative rate by flow cytometry
時間枠：Up to approximately eight weeks
|
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by flow cytometry
|
Up to approximately eight weeks
|
|
Measurable Residual Disease (MRD) negative rate by molecular testing
時間枠：Up to approximately eight weeks
|
Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by molecular testing
|
Up to approximately eight weeks
|
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
- IIT2026104
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
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。