AML (Acute Myeloid Leukemia)Phase 3NCT07712848
DEC3-VEN vs. Venetoclax-Based vs. DA Regimens in Newly Diagnosed AML
A Phase 3 study testing Arm A (VEN+"2+6"DA), Arm B (DEC3-VEN) and Arm C ("3+7"DA) in people with AML (Acute Myeloid Leukemia), run by The Second Affiliated Hospital of Kunming Medical University at 1 site in China.
Trial summary
Protocol Title: A Prospective, Randomized Controlled Study of Venetoclax Plus 3-Day Decitabine (DEC3-VEN) Versus Venetoclax Plus "2+6" DA Versus "3+7" DA Regimen in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Objective: This is a prospective, open-label, randomized, multicenter, phase II trial… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- AML (Acute Myeloid Leukemia)
- What is being tested?
- Arm A (VEN+"2+6"DA), Arm B (DEC3-VEN) and Arm C ("3+7"DA)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 291 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2026to 1 Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -
- Subjects who are suitable for enrollment in this study must meet all of the following criteria:
- Except for APL or carrying t(8) that meet the diagnostic criteria (WHO2022 criteria) of the World Health Organization; 21)/(RUNX1::RUNX1TI)、inv(16)(p13.1q22) 、 t(16; 16) (p13.1q22) 、 t(16; 16)/CBFβ::myh11) and other acute myeloid leukemia other than one of the abnormal karyotypes;
- Except for acute panmyeloproliferative disease with myelofibrosis and myeloid sarcoma, the World Health Organization AML classification is AML without separate classification;
- Newly diagnosed AML patients with male or female, age greater than or equal to 16 years old and less than 65 years old, patients are considered suitable for intensive chemotherapy;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at the time of enrollment;
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- The patient has not received previous AML therapy (except for hydroxyurea and Ara-C<1.0g/d for reducing tumor compounds);
- Pass the following laboratory test indicators (performed within 7 days before treatment):
- 1) Aspartate aminotransferase (ALT), alanine aminotransferase (AST) and alkaline phosphatase (ALP) ≤3× upper limit of normal (ULN), serum bilirubin ≤2×ULN; Serum cardiac enzymes < 2.0× ULN; Unless it is thought to be a leukemic organ involvement.
- Creatinine ≥ 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hour urine collection;
- 7. Female subjects of childbearing potential must have a negative pregnancy test result within 72 hours before the start of treatment; Not planning to become pregnant during the study and within 6 months after the last dose of study drug, and negative urine or serum pregnancy test results at screening. Men must use a latex condom during any sexual contact with WOCBP, even if they have had a successful vasectomy, and must agree to avoid childbearing (during treatment and for 6 months after the last dose of study drug).
- 8. Life expectancy exceeds 2 months;
- 9. Informed consent must be signed before the start of all specific study procedures, and the informed consent form must be signed by the patient or his immediate family; Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the legal guardian or the patient's immediate family will sign the informed consent form.
Who cannot join
- Subjects who meet any of the following criteria are not eligible for this study:
- AML with BCR-ABL1; or CML sudden change period;
- Treated patients (refers to those who have received induction chemotherapy in the past, regardless of the efficacy);
- Subjects with acute panmyelopathy with myelofibrosis or myelosarcoma as defined by WHO 2016;
- Secondary leukemia (mainly refers to those who belong to the treatment-related AML subcategory of the World Health Organization (WHO 2016) AML classification and those with a history of pre-stage MDS and/or MPD);
- Patients with other hematological diseases (such as hemophilia, myelofibrosis, etc., who are not suitable for inclusion; Those with previous blood picture abnormalities, except for bone marrow examination, MDS and MPD are allowed to be selected);
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- Pregnant or lactating patients;
- Those who are allergic to any drugs involved in this study;
- Use of strong or moderate CYP7A inducers within 3 days before the start of study treatment;
- Suffering from malignant tumors of other organs (those who need treatment);
- Obvious abnormal liver and kidney function, exceeding the enrollment criteria;
- Active cardiac disease, defined as one or more of the following:
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- Myocardial infarction less than 6 months from enrollment in the study;
- History of arrhythmias requiring medication or severe clinical symptoms;
- Uncontrolled or symptomatic congestive heart failure (> NYHA Grade 2);
- Uncontrolled or symptomatic angina;
- Left ventricular ejection fraction below the lower limit of the normal range;
- 12. Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis), known infection with human immunodeficiency virus (HIV) or active hepatitis B or C; Subjects with uncontrollable infection.
- 13. Subjects with evidence of central nervous system leukemia before treatment;
- 14. Subjects with epilepsy, dementia or other abnormal mental states that require medication and cannot understand or follow the protocol;
- 15. Restriction of oral drug intake or gastrointestinal absorption;
- 16. Those who are not suitable for enrollment in the opinion of the investigator;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650106
Zeping Zhou, +86 187 8857 1605, zhouzeping@kmmu.edu.cn
Zhou, zhouzeping@kmmu.edu.cn
About this study
Official title: A Prospective, Randomized Controlled Study on the Efficacy and Safety of Venetoclax Combined With 3-Day Decitabine (DEC3-VEN) Versus Venetoclax Combined With "2+6" DA Versus "3+7" DA Regimen in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia
Protocol Title: A Prospective, Randomized Controlled Study of Venetoclax Plus 3-Day Decitabine (DEC3-VEN) Versus Venetoclax Plus "2+6" DA Versus "3+7" DA Regimen in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Objective: This is a prospective, open-label, randomized, multicenter, phase II trial designed to compare the efficacy and safety of three induction regimens-Venetoclax plus 3-day Decitabine (DEC3-VEN), Venetoclax plus "2+6" DA, and standard "3+7" DA-in adult patients with newly diagnosed, intensifiable AML.
Read more
Study Design: The study employs a prospective, randomized, controlled, multicenter design. A total of 291 eligible patients will be enrolled across approximately 10 centers in China and randomized in a 2:2:1 ratio to the three treatment arms.
Key Eligibility Criteria:
Inclusion: Aged 16-65 with newly diagnosed non-APL AML (excluding favorable CBF-AML), eligible for intensive chemotherapy, ECOG ≤2, and adequate organ function.
Exclusion: Prior AML treatment, secondary AML, active severe infection, significant cardiac comorbidity, or known hypersensitivity to the study drugs.
Interventions:
Induction:
Arm A (VEN+"2+6"DA): Venetoclax (D1-8), Daunorubicin (D2-3), Cytarabine (D2-7).
Arm B (DEC3-VEN): Venetoclax (D1-14), Decitabine (D4-6). FLT3/ITD+ patients add Sorafenib or Gilteritinib (D8-14).
Arm C ("3+7"DA): Daunorubicin (D1-3), Cytarabine (D1-7).
Consolidation (2 cycles):
Arms A/B: Venetoclax + Intermediate-Dose Cytarabine.
Arm C: High-Dose Cytarabine.
Consolidation (Subsequent cycles):
All arms receive multiple cycles of DA or HA regimens.
Maintenance (6-8 cycles):
Arms A/B: Venetoclax + Azacitidine.
Arm C: Azacitidine.
Main Outcome Measures:
Primary Endpoint: Composite Complete Remission Rate (CR + CRi) after induction.
Secondary Endpoints: Overall Survival (OS), CR rate, MRD-negative rate, Relapse-Free Survival (RFS), Event-Free Survival (EFS), and safety.
Keywords: Acute Myeloid Leukemia, Venetoclax, Decitabine, Consolidation Therapy, Maintenance Therapy, Randomized Controlled Trial.
Read the detailed description
This Phase 3, open-label, randomized controlled trial employs a three-arm parallel design to evaluate the optimal integration of venetoclax into intensive chemotherapy for newly diagnosed AML. The study is designed to address the critical unmet need of balancing high remission rates with tolerability in fit adult AML patients.
Scientific Rationale for Treatment Arms:
Arm A (VEN+"2+6" DA) investigates a modified intensive regimen where daunorubicin exposure is limited to 2 days (vs. conventional 3 days) based on prior institutional data suggesting comparable efficacy with reduced cardiotoxicity. Arm B (DEC3-VEN) explores a novel combination of venetoclax with high-dose decitabine (20 mg/m² every 8 hours for 3 days), a regimen developed to enhance hypomethylating effects while limiting myelosuppression duration to approximately 2 weeks through shortened decitabine exposure. Arm C represents the standard "3+7" DA regimen as the reference arm.
Venetoclax Pharmacological Considerations:
The 100→200→400 mg dose ramp-up over 2-3 days is implemented for tumor lysis syndrome (TLS) prophylaxis, with extended dosing through Day 8 (Arm A) or Day 14 (Arm B) based on the pharmacokinetic principle of sustained BCL-2 inhibition. For FLT3-ITD positive patients in Arm B, sorafenib or gilteritinib is added from Day 8 to target dual oncogenic pathways.
Stratification and Randomization:
Randomization employs block randomization with stratification by study center to ensure balance across the 10 participating sites. The 2:2:1 allocation ratio (Arms A:B:C) prioritizes evaluation of the two experimental venetoclax-containing regimens while maintaining adequate power for the standard arm comparison.
MRD Assessment Methodology:
Measurable residual disease is evaluated by multi-parameter flow cytometry (sensitivity 10-⁴) and, where available, NGS-based sequencing to provide complementary sensitivity for treatment response characterization. MRD assessment is performed at remission confirmation and post-consolidation to evaluate depth of response.
Statistical Considerations:
The primary analysis employs a non-inferiority framework comparing the composite CR rate (CR+CRi) of each experimental arm against the standard arm, with a pre-specified non-inferiority margin of -10%. Hierarchical testing controls for multiplicity, prioritizing Arm A followed by Arm B comparisons. An interim analysis for futility is planned after 50% enrollment to preserve resources if either experimental arm shows <50% response rate.
- Conditions
- AML (Acute Myeloid Leukemia)
- Being tested
- Arm A (VEN+"2+6"DA), Arm B (DEC3-VEN), Arm C ("3+7"DA)
- Keywords
- Acute Myeloid Leukemia, Venetoclax, Decitabine, DA regimen, Randomized Controlled Trial
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A (VEN+"2+6"DA)Procedure or surgery
Venetoclax (Days 1-8), Daunorubicin (Days 2-3), Cytarabine (Days 2-7)
Arm B (DEC3-VEN)Procedure or surgery
Venetoclax (Days 1-14), Decitabine (Days 4-6). FLT3/ITD-positive patients receive additional Sorafenib or Gilteritinib (Days 8-14).
Arm C ("3+7"DA)Procedure or surgery
Daunorubicin (Days 1-3), Cytarabine (Days 1-7)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | (VEN+"2+6"DA) Receives: Procedure: Arm A (VEN+"2+6"DA) |
| Arm B | Experimental | (DEC3-VEN) Receives: Procedure: Arm B (DEC3-VEN) |
| Arm C | Experimental | ("3+7"DA) Receives: Procedure: Arm C ("3+7"DA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Complete Remission Rate after Induction Therapy
Percentage of patients achieving composite complete remission (CR + CRi) after induction therapy (defined as the first 28-day cycle of treatment). Complete remission (CR) and CR with incomplete hematologic recovery (CRi) are defined according to the European LeukemiaNet (ELN) 2022 criteria. Response is assessed by bone marrow aspiration and biopsy performed at a central laboratory between Day 21 and Day 28 of the induction cycle (or upon count recovery). The measurement unit is the percentage of patients achieving CR or CRi among all randomized patients (intention-to-treat population).
Measured: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes (5)
Overall Survival (OS)
Time from randomization to death from any cause (Overall Survival)， assessed using the Kaplan-Meier method， with the difference between treatment groups evaluated by the stratified log-rank test. The measurement unit is months.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
MRD-negative remission rate
Percentage of patients achieving measurable residual disease (MRD) negativity， assessed by multiparameter flow cytometry (MFC) with a sensitivity threshold of 0.1% (10-³) in patients who achieved CR/CRi.
Measured: At the end of Cycle 1 (each cycle is 28 days)
Relapse-Free Survival (RFS)
Time from first documented CR/CRi to confirmed hematologic relapse or death. Relapse defined per ELN 2022 criteria. Assessed by Kaplan-Meier method. Reported as median months with 95% CI.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Event-Free Survival (EFS)
Event-free survival， defined as the time from randomization to treatment failure (failure to achieve CR/CRi within 6 cycles)， confirmed relapse， or death from any cause， whichever occurs first， assessed using the Kaplan-Meier method. The measurement unit is months.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
safety profile
Incidence of treatment-emergent adverse events (TEAEs)， assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The measurement unit is the percentage of patients experiencing each grade of adverse event. Incidence of serious adverse events (SAEs)， assessed using the NCI CTCAE version 5.0， with events defined as those leading to death， life-threatening， requiring hospitalization， or causing significant disability.Incidence of grade ≥3 infections， including pneumonia， sepsis， and febrile neutropenia， assessed using the NCI CTCAE version 5.0.
Measured: At the end of Cycle 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2026
- Study start1 Apr 2026
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AML (Acute Myeloid Leukemia)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 291 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Second Affiliated Hospital of Kunming Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chines, Department of Hematology, Oncology Center, Tianjin Union Medical Center of Nankai University, Department of Hematology, Handan Central Hospital, Department of Hematology, The Affiliated Tai'an City Central Hospital of Qingdao University, Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Department of Hematology, The Second Xiangya Hospital, Central South University, Department of Hematology, Guizhou Provincial People's Hospital, People's Hospital of Guangxi Zhuang Autonomous Region, Affiliated Hospital of Qinghai University
- Responsible party
- Principal investigator, ZePing Zhou, The Second Affiliated Hospital of Kunming Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07712848
- Sponsor's protocol ID
- 2ndKunmingMC
- Status last verified
- Jul 2026
- First submitted
- 17 Mar 2026
- Last updated
- 20 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mantzaris I, Goldfinger M, Uriel M, Shastri A, Shah N, Gritsman K, Kornblum NS, Shapiro L, Sica RA, Munoz A, Chambers N, Dhawan A, Verceles JA, Fehn K, Tirone B, Shah L, Clark S, Zhang C, Kim M, Cooper DL, Verma A, Konopleva M, Feldman EJ. Venetoclax plus daunorubicin and cytarabine for newly diagnosed acute myeloid leukemia: results of a phase 1b study. Blood. 2025 Apr 24;145(17):1870-1875. doi: 10.1182/blood.2024026700.
PubMed 39919267Suo X, Fang Z, Wang D, Zhao L, Liu J, Li H, Ma X, Zhang C, Zhao X, Shi R, Wu Y, Jiao Z, Song J, Zhang L, Li L, Zhang S, Lu X, Yuan L, Gao S, Zhang J, Liu K, Zhao X, Bai G, Mi Y. Venetoclax combined with daunorubicin and cytarabine (2 + 6) in acute myeloid leukemia: Updated results of a phase II trial. Hematol Oncol. 2024 Jul;42(4):e3296. doi: 10.1002/hon.3296. No abstract available.
PubMed 39041653Mei M, Aldoss I, Marcucci G, Pullarkat V. Hypomethylating agents in combination with venetoclax for acute myeloid leukemia: Update on clinical trial data and practical considerations for use. Am J Hematol. 2019 Mar;94(3):358-362. doi: 10.1002/ajh.25369. Epub 2018 Dec 13.
PubMed 30499168Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 2003 Mar 15;101(6):2125-31. doi: 10.1182/blood-2002-06-1714. Epub 2002 Nov 7.
PubMed 12424199