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.
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 1단계
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Dose-Limiting Toxicity (DLT)
기간: 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
기간: 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
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Complete remission (CR) rate
기간: 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
기간: 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
기간: Up to approximately eight weeks
|
Proportion of patients with morphologic leukemia-free state (MLFS)
|
Up to approximately eight weeks
|
|
Event-free survival (EFS)
기간: 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)
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- IIT2026104
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
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미국 FDA 규제 기기 제품 연구
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