Early T Acute Lymphoblastic LeukemiaPhase 2NCT07012447
Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations
A Phase 2 study testing Venetoclax, Azacitidine and Cytarabine in people with Early T Acute Lymphoblastic Leukemia and T-Acute Lymphoblastic Leukemia, run by yuejun Liu at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate the efficacy and safety of venetoclax combined with azacitidine in treating newly diagnosed early T-cell precursor (ETP)-like acute lymphoblastic leukemia (ALL), T-ALL with myeloid mutations, or T/myeloid mixed-phenotype acute leukemia (T/My-MPAL). Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Early T Acute Lymphoblastic Leukemia, T-Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T/Myeloid, Nos
- What is being tested?
- Venetoclax, Azacitidine and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2025to 1 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- No gender restrictions
- Age ≥ 14 years
- Confirmed diagnosis of one of the following:
- ETP-like leukemia (CD7⁺, CD1a-, CD8-, with CD5 expression stratified as ETP-ALL ≤75% or Near-ETP-ALL >75%) T-cell acute lymphoblastic leukemia (T-ALL) with myeloid mutations (including FLT3, DNMT3A, STAG2, IDH1/2, RUNX1, EZH2, WT1, ASXL1/2, SF3B1, TET2, BCOR, BCORL1, and MLL-PTD) T/myeloid mixed phenotype acute leukemia (T/My-MPAL) (with concurrent T-lineage and myeloid markers, e.g., cCD3⁺/mCD3⁺, CD7⁺, MPO⁺)
- Newly diagnosed patients without prior induction therapy Limited prior therapy allowed: hydroxyurea, dexamethasone, or low-dose cytarabine/venetoclax (cumulative dose <0.5g), and leukocytapheresis
- Expected survival time ≥ 3 months
- Liver function: total bilirubin ≤ 2× ULN; ALT/AST ≤ 3× ULN (or ≤ 5× ULN if liver infiltration by leukemia is present) ; Renal function: endogenous creatinine clearance ≥ 30 ml/min; Cardiac function: left ventricular ejection fraction > 45%
- Demonstrated capacity to understand the study and willingness to provide informed consent
Who cannot join
- Presence of recurrent genetic abnormalities such as t(8;21), t(15;17), inv(16)/t(16;16) leukemia
- Prior hypersensitivity to study drugs or compounds of similar chemical structure
- Active uncontrolled infections as determined by the investigator
- Active bleeding
- Recent history (within 1 year) of thrombosis, embolism, or cerebral hemorrhage
- Pregnancy, breastfeeding, or unwillingness to use contraception in women of childbearing potential
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- Drug addiction or chronic alcoholism that could interfere with trial evaluation
- Psychiatric disorders or other conditions that would prevent obtaining informed consent or compliance with trial requirements
- Any condition deemed unsuitable for trial participation by 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
Ethical Committee of the First Affliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Zhou-lin Lu, 008613914086271
About this study
Official title: Evaluating the Efficacy of Venetoclax Combined With Azacitidine Induction Therapy of Early T-cell Precursor-like Acute Lymphoblastic Leukemia and T-ALL With Myeloid Mutations
The goal of this clinical trial is to evaluate the efficacy and safety of venetoclax combined with azacitidine in treating newly diagnosed early T-cell precursor (ETP)-like acute lymphoblastic leukemia (ALL), T-ALL with myeloid mutations, or T/myeloid mixed-phenotype acute leukemia (T/My-MPAL).
Participant population: Patients aged ≥14 years diagnosed with ETP-like leukemia, T-ALL with myeloid mutations, or T/My-MPAL, regardless of sex/gender.
Read more
The main question it aims to answer: Does venetoclax plus azacitidine achieve a significantly higher overall response rate (ORR: CR + CRi) compared to historical controls (54% vs. 90%) after two induction cycles?
Comparison group: Researchers will compare ORR outcomes to historical data from conventional chemotherapy regimens to assess treatment superiority.
Participants will:
- Receive two 28-day cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m²/day SC, D1-7).
- Undergo serial bone marrow biopsies, blood tests, and imaging (e.g., PET-CT) for response assessment.
- Follow dose adjustment protocols for toxicity management (e.g., neutropenia, thrombocytopenia).
Read the detailed description
This study addresses the unmet need for effective therapies in high-risk T-ALL subtypes, including ETP-like leukemia and T/My-MPAL, which exhibit myeloid-like genetic profiles (e.g., FLT3, DNMT3A, RUNX1 mutations) and poor outcomes under conventional chemotherapy (5-year OS <40%). Preclinical and pilot clinical data demonstrate that venetoclax, a BCL-2 inhibitor, synergizes with azacitidine, a hypomethylating agent, to induce apoptosis in leukemia stem cells by targeting oxidative phosphorylation and epigenetic dysregulation. Building on a pilot study, this Phase II trial employs a single-arm design to validate efficacy in a larger cohort.
Patients receive two induction cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7), with response assessed via bone marrow morphology, flow cytometry, and molecular testing (Days 22-35).
Early Efficacy Evaluation: After the first induction cycle (Days 22-35), response is assessed via bone marrow morphology, flow cytometry, and molecular profiling.
Stopping Criteria:
Patients failing to achieve at least partial remission (PR) after Cycle 1 will be withdrawn from the study.
Patients failing to achieve CR or CRi at the end of Cycle 2 will also discontinue study treatment.
Consolidation strategies include allo-HSCT or high dose cytarabine (HiDAC) for fit patients or maintenance therapy for unfit individuals.
Rigorous safety monitoring follows NCI-CTCAE v5.0 criteria, with dose adjustments for hematologic/non-hematologic toxicities.
Statistical analysis includes intent-to-treat and per-protocol populations, with ORR analyzed via exact binomial tests and survival endpoints via Kaplan-Meier/Cox regression. The study integrates translational biomarkers (e.g., BCL-2 expression, mutational profiling) to identify predictors of response, aiming to establish a novel, mechanism-driven regimen for these aggressive leukemias.
- Conditions
- Early T Acute Lymphoblastic Leukemia, T-Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T/Myeloid, Nos
- Being tested
- Venetoclax, Azacitidine, Cytarabine
- Keywords
- Adverse risk, newly diagnosed, induction therapy
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute, Pyloric Stenosis, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called Venclexta
Orally by mouth
AzacitidineDrug
Subcutaneous injection
CytarabineDrug
Also called Ara-C
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Investigational ( venetoclax, azacytidine) | Experimental | Two cycles induction as venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7); Consolidation: For fit patients, if those with MRD (Minimal Residual Disease) are negative or refuse to undergo allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m² q12h, days 1-3) cytarabine-based therapy is administered for 3-4 cycles; if patients are MRD-positive, they undergo allo-HSCT.
For unfit patients, each venetoclax combined with azacitidine treatment cycle is anticipated to be 28 days in length until progression of disease, although cycle delays may occur due to delayed blood count recovery. Receives: Drug: Venetoclax; Drug: Azacitidine; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) after two treatment cycles of induction therapy
Rates of complete remission (CR), and complete remission with incomplete hematologic recovery (CRi)
Measured: time from the date of enrollment to 2 cycles of induction before consolidation therapy（100 days）
Secondary outcomes (5)
OS: overall survival
time from the date of enrollment to death from any cause or the last follow-up
Measured: 2 years
LFS：leukemia-free survival
the duration from the date of enrollment to the occurrence of treatment failure, relapse, death from any cause, or the last follow-up.
Measured: 2 years
DOR: duration of remission
Time between the first remission and relapse
Measured: 2 years
AE
Adverse events during the induction treatment.
Measured: Within 60 days after treatment
Volume of infused blood products
The volume of infused blood products during the induction treatment.
Measured: Within 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2025
- Study start1 Apr 2025
- Primary completion1 Apr 2027 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early T Acute Lymphoblastic LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- yuejun Liu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, yuejun Liu, The First Affiliated Hospital of Soochow University
- Investigators
- Yue-jun Liu, Principal investigator, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07012447
- Sponsor's protocol ID
- SZ-ETP01
- Status last verified
- Jun 2025
- First submitted
- 21 Apr 2025
- Last updated
- 10 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Efficacy of Venetoclax Combined With Azacitidine Induction Therapy of Early T-cell Precursor-like Acute Lymphoblastic Leukemia and T-ALL With Myeloid Mutations
- ClinicalTrials.gov ID
- NCT07012447
- Acronym / sponsor ID
- SZ-ETP01
- Conditions
- Early T Acute Lymphoblastic Leukemia, T-Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T/Myeloid, Nos
- Keywords
- Adverse risk, newly diagnosed, induction therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- yuejun LiuUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 10 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the efficacy and safety of venetoclax combined with azacitidine in treating newly diagnosed early T-cell precursor (ETP)-like acute lymphoblastic leukemia (ALL), T-ALL with myeloid mutations, or T/myeloid mixed-phenotype acute leukemia (T/My-MPAL).
Participant population: Patients aged ≥14 years diagnosed with ETP-like leukemia, T-ALL with myeloid mutations, or T/My-MPAL, regardless of sex/gender.
The main question it aims to answer: Does venetoclax plus azacitidine achieve a significantly higher overall response rate (ORR: CR + CRi) compared to historical controls (54% vs. 90%) after two induction cycles?
Comparison group: Researchers will compare ORR outcomes to historical data from conventional chemotherapy regimens to assess treatment superiority.
Participants will:
- Receive two 28-day cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m²/day SC, D1-7).
- Undergo serial bone marrow biopsies, blood tests, and imaging (e.g., PET-CT) for response assessment.
- Follow dose adjustment protocols for toxicity management (e.g., neutropenia, thrombocytopenia).
Detailed description
This study addresses the unmet need for effective therapies in high-risk T-ALL subtypes, including ETP-like leukemia and T/My-MPAL, which exhibit myeloid-like genetic profiles (e.g., FLT3, DNMT3A, RUNX1 mutations) and poor outcomes under conventional chemotherapy (5-year OS <40%). Preclinical and pilot clinical data demonstrate that venetoclax, a BCL-2 inhibitor, synergizes with azacitidine, a hypomethylating agent, to induce apoptosis in leukemia stem cells by targeting oxidative phosphorylation and epigenetic dysregulation. Building on a pilot study, this Phase II trial employs a single-arm design to validate efficacy in a larger cohort.
Patients receive two induction cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7), with response assessed via bone marrow morphology, flow cytometry, and molecular testing (Days 22-35).
Early Efficacy Evaluation: After the first induction cycle (Days 22-35), response is assessed via bone marrow morphology, flow cytometry, and molecular profiling.
Stopping Criteria:
Patients failing to achieve at least partial remission (PR) after Cycle 1 will be withdrawn from the study.
Patients failing to achieve CR or CRi at the end of Cycle 2 will also discontinue study treatment.
Consolidation strategies include allo-HSCT or high dose cytarabine (HiDAC) for fit patients or maintenance therapy for unfit individuals.
Rigorous safety monitoring follows NCI-CTCAE v5.0 criteria, with dose adjustments for hematologic/non-hematologic toxicities.
Statistical analysis includes intent-to-treat and per-protocol populations, with ORR analyzed via exact binomial tests and survival endpoints via Kaplan-Meier/Cox regression. The study integrates translational biomarkers (e.g., BCL-2 expression, mutational profiling) to identify predictors of response, aiming to establish a novel, mechanism-driven regimen for these aggressive leukemias.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Investigational ( venetoclax, azacytidine) | Experimental | Drug: Venetoclax, Drug: Azacitidine, Drug: CytarabineTwo cycles induction as venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7); Consolidation: For fit patients, if those with MRD (Minimal Residual Disease) are negative or refuse to undergo allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m² q12h, days 1-3) cytarabine-based therapy is administered for 3-4 cycles; if patients are MRD-positive, they undergo allo-HSCT. For unfit patients, each venetoclax combined with azacitidine treatment cycle is anticipated to be 28 days in length until progression of disease, although cycle delays may occur due to delayed blood count recovery. |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- No gender restrictions
- Age ≥ 14 years
- Confirmed diagnosis of one of the following:
- ETP-like leukemia (CD7⁺, CD1a-, CD8-, with CD5 expression stratified as ETP-ALL ≤75% or Near-ETP-ALL >75%) T-cell acute lymphoblastic leukemia (T-ALL) with myeloid mutations (including FLT3, DNMT3A, STAG2, IDH1/2, RUNX1, EZH2, WT1, ASXL1/2, SF3B1, TET2, BCOR, BCORL1, and MLL-PTD) T/myeloid mixed phenotype acute leukemia (T/My-MPAL) (with concurrent T-lineage and myeloid markers, e.g., cCD3⁺/mCD3⁺, CD7⁺, MPO⁺)
- Newly diagnosed patients without prior induction therapy Limited prior therapy allowed: hydroxyurea, dexamethasone, or low-dose cytarabine/venetoclax (cumulative dose <0.5g), and leukocytapheresis
Key exclusion criteria (9 listed)
- Presence of recurrent genetic abnormalities such as t(8;21), t(15;17), inv(16)/t(16;16) leukemia
- Prior hypersensitivity to study drugs or compounds of similar chemical structure
- Active uncontrolled infections as determined by the investigator
- Active bleeding
- Recent history (within 1 year) of thrombosis, embolism, or cerebral hemorrhage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxAlso: VenclextaOrally by mouth | Drug | Investigational ( venetoclax, azacytidine) |
| AzacitidineSubcutaneous injection | Drug | Investigational ( venetoclax, azacytidine) |
| CytarabineAlso: Ara-CIntravenous infusion | Drug | Investigational ( venetoclax, azacytidine) |
Primary outcome
Overall response rate (ORR) after two treatment cycles of induction therapy
Time frame: time from the date of enrollment to 2 cycles of induction before consolidation therapy（100 days）
Rates of complete remission (CR), and complete remission with incomplete hematologic recovery (CRi)
5 secondary outcomes
OS: overall survival
Time frame: 2 years
LFS：leukemia-free survival
Time frame: 2 years
DOR: duration of remission
Time frame: 2 years
AE
Time frame: Within 60 days after treatment
Volume of infused blood products
Time frame: Within 60 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yue-jun Liu principal investigator
The First Affiliated Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Venetoclax, Azacitidine and Cytarabine in people with Early T Acute Lymphoblastic Leukemia and T-Acute Lymphoblastic Leukemia, run by yuejun Liu at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yue-jun Liu (008613915535177, liuyuejun@suda.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) after two treatment cycles of induction therapy (time frame: time from the date of enrollment to 2 cycles of induction before consolidation therapy（100 days）). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2025.