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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Venetoclax plus Azacitidine (VA regimen) | Experimental |
|
|
| "3+7" induction chemotherapy | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VEN combined with azacitidine | Drug | Venetoclax,oral targeted anti-BCL-2 agent and Azacitidine,hypomethylating agent, given via injection for experimental VA arm only |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite complete remission rate at the end of induction cycle | At the end of 1-2 induction treatment cycles (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Composite Complete Remission | At the end of 1-2 induction treatment cycles (each cycle is 28 days) | |
| Minimal residual disease (MRD) negative rate after remission | At the end of induction cycle (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 |
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:
Participants must have the ability to understand and be willing to participate in this study, and sign an informed consent form.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yang Shen, MD | Contact | +86-021-64370045 | sy_clinicaltrial@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Yang Shen, MD | Ruijin Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ruijin Hospital, Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | 200025 | China |
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| Cytarabine plus Daunorubicin | Drug | Cytarabine,continuous intravenous infusion for total 7 days and Daunorubicin,Intravenous anthracycline chemotherapy administered for 3 days,in standard 3+7 induction regimen |
|
| Duration of Response (DoR) | From date of confirmed complete response (CR) until documented disease relapse or death from any cause, assessed up to 24 months after randomization |
| 1-year Event-Free Survival (EFS) rate | 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 |
| 1-year Overall Survival (OS) rate | 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 |
| 1-year recurrence free survival rate | 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 |
| Safety profile during induction therapy | 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. | From initiation of induction therapy through the end of the induction treatment period,assessed up to 8 weeks after randomization |
| Hospitalization duration during induction therapy | From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days) |
| Transfusion volume during induction therapy | From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days) |
| Medical cost during induction therapy | From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days) |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D003561 | Cytarabine |
| D003630 | Daunorubicin |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D001087 | Arabinonucleosides |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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