Study on the Efficacy and Safety of VA Regimen Compared to "3+7" Regimen in Newly Diagnosed AML With NPM1 or IDH1/IDH2 Mutations
A Prospective, Multicenter, Randomized Controlled, Open Label, Non-Inferiority Study Comparing the Efficacy and Safety of the VA Regimen (Venetoclax Combined With Azacitidine) With the "3+7" Regimen in the Treatment of Newly Diagnosed AML Patients With NPM1 or IDH1/IDH2 Mutations
This prospective, multicenter, randomized, open-label, non-inferiority clinical study aims to compare the efficacy and safety of VA regimen (venetoclax combined with azacitidine) versus conventional "3+7" chemotherapy regimen in adult patients aged 18 to 65 years with newly diagnosed acute myeloid leukemia (AML) carrying NPM1, IDH1 or IDH2 gene mutations.
The primary goal of this trial is to check whether the VA treatment can reach a non-inferior composite complete remission rate at the end of the induction treatment cycle, which is the key primary endpoint of this research. Several secondary clinical outcomes will also be evaluated in this study, including the rate of minimal residual disease (MRD) negativity after remission, duration of remission, 1-year event-free survival rate and 1-year overall survival rate of enrolled patients. In addition, the safety and treatment-related side effects occurring during the whole induction treatment phase will be systematically collected and compared between two groups as another important secondary assessment.
Eligible enrolled participants will be randomly split into two study groups: patients in experimental group will receive venetoclax plus azacitidine (VA regimen), while patients in control group will receive standard "3+7" induction chemotherapy following conventional clinical protocol. All subjects will complete regular disease assessment, laboratory examinations and scheduled follow-up visits as required by trial design during treatment and post-treatment observation period.
Researchers will collect and analyze all above clinical outcome data from all participants, to verify the non-inferior efficacy and relative safety of VA regimen for this specific subtype of newly diagnosed AML patients.
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Yang Shen, MD
- 전화번호: +86-021-64370045
- 이메일: sy_clinicaltrial@163.com
연구 장소
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Shanghai Municipality
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Shanghai, Shanghai Municipality, 중국, 200025
- Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
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연락하다:
- Yang Shen, MD
- 전화번호: +86-021-64370045
- 이메일: sy_clinicaltrial@163.com
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Age ≥ 65 years old ≥ 18 years old;
- Diagnosed as acute myeloid leukemia (non APL) (diagnostic criteria refer to the 2022 ELN classification system);
- Initial diagnosis accompanied by NPM1 mutations (A, B, D types and rare types are all acceptable) and/or IDH1/IDH2 mutations;
- Have not received any other induction therapy before (except hydroxyurea);
- Physical fitness status score (ECOG PS) 0-3;
Having sufficient organ function, defined as follows:
- Liver function: serum total bilirubin ≤ 3 x upper limit of normal range (ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3 x ULN, unless considered to be caused by leukemia;
- Renal function: endogenous creatinine clearance rate ≥ 30ml/min;
- Heart function: NYHA classification ≤ 2 points;
- Participants must have the ability to understand and be willing to participate in this study, and sign an informed consent form.
Exclusion Criteria:
- Acute promyelocytic leukemia;
- Merge extramedullary infiltration such as central nervous system leukemia;
- Have a clear history of CMML or MDS, and later progress to AML; Or have a history of malignant tumors;
- There is uncontrolled active infection (including bacterial, fungal, or viral infections);
- Pregnant or lactating women;
- Researchers determine that participants are not suitable to participate in this experiment
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Venetoclax plus Azacitidine (VA regimen)
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Venetoclax,oral targeted anti-BCL-2 agent and Azacitidine,hypomethylating agent, given via injection for experimental VA arm only
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활성 비교기: "3+7" induction chemotherapy
Standard 3+7 induction chemotherapy (Cytarabine continuous infusion for 7 days plus Anthracycline intravenous infusion for 3 days) following routine clinical induction regimen for AML.
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Cytarabine,continuous intravenous infusion for total 7 days and Daunorubicin,Intravenous anthracycline chemotherapy administered for 3 days,in standard 3+7 induction regimen
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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Composite complete remission rate at the end of induction cycle
기간: At the end of 1-2 induction treatment cycles (each cycle is 28 days)
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At the end of 1-2 induction treatment cycles (each cycle is 28 days)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Composite Complete Remission
기간: At the end of 1-2 induction treatment cycles (each cycle is 28 days)
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At the end of 1-2 induction treatment cycles (each cycle is 28 days)
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Minimal residual disease (MRD) negative rate after remission
기간: At the end of induction cycle (each cycle is 28 days)
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At the end of induction cycle (each cycle is 28 days)
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Duration of Response (DoR)
기간: From date of confirmed complete response (CR) until documented disease relapse or death from any cause, assessed up to 24 months after randomization
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From date of confirmed complete response (CR) until documented disease relapse or death from any cause, assessed up to 24 months after randomization
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1-year Event-Free Survival (EFS) rate
기간: From date of randomization until first documented treatment failure, relapse, or death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization
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From date of randomization until first documented treatment failure, relapse, or death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization
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1-year Overall Survival (OS) rate
기간: From date of randomization until death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization
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From date of randomization until death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization
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1-year recurrence free survival rate
기간: From date of randomization until first confirmed disease recurrence or death from any cause, assessed up to 24 months after randomization; the 1-year rate will be calculated at the 12-month timepoint after randomization
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From date of randomization until first confirmed disease recurrence or death from any cause, assessed up to 24 months after randomization; the 1-year rate will be calculated at the 12-month timepoint after randomization
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Safety profile during induction therapy
기간: From initiation of induction therapy through the end of the induction treatment period,assessed up to 8 weeks after randomization
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Evaluate the incidence of grade 3 and grade 4 adverse events classified per CTCAE Version 5.0, the duration of severe adverse events, type, frequency and management of all treatment-emergent adverse events occurring during the induction treatment phase.
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From initiation of induction therapy through the end of the induction treatment period,assessed up to 8 weeks after randomization
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기타 결과 측정
결과 측정 |
기간 |
|---|---|
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Correlation between baseline AML gene mutation status detected by next-generation sequencing and anti-leukemic efficacy endpoints (complete remission rate, MRD-negative rate, 1-year recurrence-free survival rate) in VA regimen arm
기간: From date of randomization up to 24 months after randomization, biomarker-efficacy correlation analysis will be performed using clinical data collected within the first 12 months post randomization
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From date of randomization up to 24 months after randomization, biomarker-efficacy correlation analysis will be performed using clinical data collected within the first 12 months post randomization
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Hospitalization duration during induction therapy
기간: From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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Transfusion volume during induction therapy
기간: From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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Medical cost during induction therapy
기간: From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)
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공동 작업자 및 조사자
스폰서
수사관
- 수석 연구원: Yang Shen, MD, Ruijin Hospital
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
- NPM1/IDH-AML01
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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