Acute Myeloid Leukemia With T(8;21)(Q22;Q22)Phase 1/2NCT07028073
A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia
A Phase 1/2 study testing Group A (FIT): Avapritinib + IA regimen and Group B (UNFIT): Avapritinib + VA regimen in people with Acute Myeloid Leukemia With T(8;21)(Q22;Q22) and Acute Myeloid Leukemia With T(16;16)(P13;Q22), run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
The goal of this clinical trial is to learn if avapritinib combined with standard induction therapy works to treat newly diagnosed adult acute myeloid leukemia (AML) patients with KIT mutations and t(8;21)(q22;q22.1); inv(16)(p13.1q22) or t(16;16)(p13.1;q22). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With T(8;21)(Q22;Q22), Acute Myeloid Leukemia With T(16;16)(P13;Q22), KIT Gene Mutation
- What is being tested?
- Group A (FIT): Avapritinib + IA regimen and Group B (UNFIT): Avapritinib + VA regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteChina
- Study dates
- 15 May 2025to 31 Dec 2027
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years, both genders
- Diagnosis of acute myeloid leukemia according to WHO 2022 criteria
- Treatment-naive patients (hydroxyurea or low-dose cytarabine <0.5g cumulative dose allowed)
- Bone marrow detection of KIT mutations with concurrent t(8;21)(q22;q22.1) or RUNX1::RUNX1T1 fusion gene; or inv(16)(p13.1q22) or t(16;16)(p13.1;q22) or CBFβ::MYH11 fusion gene
- Life expectancy >12 weeks Group A: ≥18 and <65 years with ECOG 0-1; Group B: ≥65 years or ≥18 and <65 years with comorbidities (ECOG ≥2, cardiac disease, creatinine clearance 30-50ml/min, or mild hepatic impairment)
- Adequate organ function: bilirubin ≤2×ULN, ALT/AST ≤3×ULN (≤5×ULN if leukemic infiltration), creatinine clearance ≥30ml/min, left ventricular ejection fraction >45%
Who cannot join
- Known hypersensitivity to KIT inhibitors, cytarabine, idarubicin, venetoclax, azacitidine or similar agents
- Concurrent use of other KIT inhibitors (dasatinib, sorafenib, gilteritinib, midostaurin)
- Intracranial hemorrhage on imaging or unresolved prior intracranial bleeding
- Active uncontrolled infection
- Significant organ dysfunction: myocardial infarction, chronic heart failure, decompensated liver dysfunction, renal failure
- Pregnancy or breastfeeding
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 First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Su-ning Chen, M.D., +8613814881746, chensuning@sina.com
About this study
Official title: Avapritinib Combined With Standard Therapy for the Treatment of Newly Diagnosed KIT Mutation Acute Myeloid Leukemia With t(8;21)(q22;q22.1); Inv(16)(p13.1q22) or t(16;16)(p13.1;q22): a Prospective, Multi-center, Single-arm, Two-cohorts Study
The goal of this clinical trial is to learn if avapritinib combined with standard induction therapy works to treat newly diagnosed adult acute myeloid leukemia (AML) patients with KIT mutations and t(8;21)(q22;q22.1); inv(16)(p13.1q22) or t(16;16)(p13.1;q22). It will also investigate the safety and tolerability of this combination therapy. The main questions it aims to answer are:
To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of avapritinib combined with chemotherapy by Dose-limiting toxicity (DLT).
Does this combination therapy improve the rates of minimal residual disease (MRD) negativity and long-term survival outcomes?
Read the detailed description
The prognosis of CBF-AML patients with KIT mutation remains relatively poor. CBF-AML is a heterogeneous disease in which many altered molecular pathways could contribute to the prognosis of the disease. Thus, curative approaches have been based on standard and high-dose cytarabine regimens using high-dose chemotherapy. However, the high rate of relapses in these patients should stimulate the development of new regimens. In recent years, there has been a series of new drugs under development that allow the design of combination therapies in this population. These drugs have an acceptable toxicity profile and are able to improve the CR rate in this population. In this way, the standard therapy and a small molecular targeted agent (Avapritinib) could produce a powerful antileukemic effect, preventing the adaptive escape mechanisms of leukemic cells. The investigators have designed a phase I-II trial based on the combination of a three-drug regimen (IA: standard-dose cytarabine + darubicin) or (VA: Azacitidine + Venetoclax) combined with avapritinib, which in this population could be well tolerated by a sequential type administration. The first objective is to achieve rapid control of the disease and the recommended dose for Phase II, using two different schemes, one based on IA and the other on VA, by dose escalation in Phase I of the trial. The second goal is to prevent relapse through a consolidation and maintenance schedule. Phase II will study the efficacy and safety of the recommended dose for Phase II.
- Conditions
- Acute Myeloid Leukemia With T(8;21)(Q22;Q22), Acute Myeloid Leukemia With T(16;16)(P13;Q22), KIT Gene Mutation, Avapritinib
- Being tested
- Group A (FIT): Avapritinib + IA regimen, Group B (UNFIT): Avapritinib + VA regimen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group A (FIT): Avapritinib + IA regimenDrug
Also called Group A (Intensive chemotherapy)
Cytarabine 100mg/m² days 1-7 Idarubicin 12mg/m² days 1-3 Avapritinib orally on days 8-21 (28-day cycle)
Group B (UNFIT): Avapritinib + VA regimenDrug
Also called Group B (Non-intensive chemotherapy)
Venetoclax 100mg day 1, 200mg day 2, 400mg days 3-28 Azacitidine 75mg/m² days 1-7 Avapritinib orally on days 8-21 (28-day cycle)
| Study group | Role | What they receive |
|---|---|---|
| Group A (FIT): Avapritinib Combined Intensive Chemotherapy in patients with newly diagnosed AML | Experimental | Not described Receives: Drug: Group A (FIT): Avapritinib + IA regimen |
| Group B (UNFIT): Avapritinib Combined Venetoclax/Azacitidine in patients with newly diagnosed AML | Experimental | Not described Receives: Drug: Group B (UNFIT): Avapritinib + VA regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Recommended phase 2 dose (RP2D)
Recommended phase 2 dose (RP2D) of IA-based and VA-based combination with avapritinib schedules
Measured: Approximately 6 months after first patient first visit (FPFV)
Phase II: MRD (Measure residual disease) negativity rate
MRD negativity rate - proportion of patients achieving ≥3-log reduction in RUNX1::RUNX1T1 or CBFβ::MYH11 fusion gene levels by qPCR between the 1st and 2nd consolidation courses.
Measured: Aproximatey 2 years after FPFV
Secondary outcomes (3)
Overall survival (OS)
Overall survival will be defined as the number of days from the start of treatment to the date of death. Subjects that have not died will be censored at the last known date to be alive. To estimate 1, 2 and 3 years progression-free survival.
Measured: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
Composite complete remission rate (CRc)
Composite complete remission rate (CRc) after one cycle of induction therapy
Measured: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
Adverse Event
Safety profile: incidence of grade 3-4 clinical adverse events and laboratory abnormalities
Measured: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study start15 May 2025
- Primary completion15 May 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia With T(8;21)(Q22;Q22)Studies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Soochow UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Phase 1: Study treatment will start at level 1, and the therapeutic level will be escalated or descalated depending on the appearance of DLT. DLT will be monitored during cycle 1. Phase I will consist of two parallel dose escalation cohorts, with consecutive assignment to each group. For the dose escalation, we will use two parallel groups following a standard "3+3" design. Patients will be assigned sequentially to each group: Group A receives avapritinib with the IA regimen for fit patients, and Group B receives the VA regimen for those unfit. Phase II includes two treatment arm groups (IA-based RP2D vs. VA-based RP2D). Patients will be enrolled at diagnosis, within a maximum 28-day screening period, and will be assessed for eligibility for intensive therapy and therefore assigned to a treatment arm. All screening activities will be performed after the patient's informed consent form is signed.
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Suning, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07028073
- Sponsor's protocol ID
- SZ-AML03
- Status last verified
- Jun 2025
- First submitted
- 11 Jun 2025
- Last updated
- 19 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Avapritinib Combined With Standard Therapy for the Treatment of Newly Diagnosed KIT Mutation Acute Myeloid Leukemia With t(8;21)(q22;q22.1); Inv(16)(p13.1q22) or t(16;16)(p13.1;q22): a Prospective, Multi-center, Single-arm, Two-cohorts Study
- ClinicalTrials.gov ID
- NCT07028073
- Acronym / sponsor ID
- SZ-AML03
- Conditions
- Acute Myeloid Leukemia With T(8;21)(Q22;Q22), Acute Myeloid Leukemia With T(16;16)(P13;Q22), KIT Gene Mutation, Avapritinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 15 May 2025 (actual)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 19 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 learn if avapritinib combined with standard induction therapy works to treat newly diagnosed adult acute myeloid leukemia (AML) patients with KIT mutations and t(8;21)(q22;q22.1); inv(16)(p13.1q22) or t(16;16)(p13.1;q22). It will also investigate the safety and tolerability of this combination therapy. The main questions it aims to answer are:
To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of avapritinib combined with chemotherapy by Dose-limiting toxicity (DLT).
Does this combination therapy improve the rates of minimal residual disease (MRD) negativity and long-term survival outcomes?
Detailed description
The prognosis of CBF-AML patients with KIT mutation remains relatively poor. CBF-AML is a heterogeneous disease in which many altered molecular pathways could contribute to the prognosis of the disease. Thus, curative approaches have been based on standard and high-dose cytarabine regimens using high-dose chemotherapy. However, the high rate of relapses in these patients should stimulate the development of new regimens. In recent years, there has been a series of new drugs under development that allow the design of combination therapies in this population. These drugs have an acceptable toxicity profile and are able to improve the CR rate in this population. In this way, the standard therapy and a small molecular targeted agent (Avapritinib) could produce a powerful antileukemic effect, preventing the adaptive escape mechanisms of leukemic cells. The investigators have designed a phase I-II trial based on the combination of a three-drug regimen (IA: standard-dose cytarabine + darubicin) or (VA: Azacitidine + Venetoclax) combined with avapritinib, which in this population could be well tolerated by a sequential type administration. The first objective is to achieve rapid control of the disease and the recommended dose for Phase II, using two different schemes, one based on IA and the other on VA, by dose escalation in Phase I of the trial. The second goal is to prevent relapse through a consolidation and maintenance schedule. Phase II will study the efficacy and safety of the recommended dose for Phase II.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase 1: Study treatment will start at level 1, and the therapeutic level will be escalated or descalated depending on the appearance of DLT. DLT will be monitored during cycle 1. Phase I will consist of two parallel dose escalation cohorts, with consecutive assignment to each group. For the dose escalation, we will use two parallel groups following a standard "3+3" design. Patients will be assigned sequentially to each group: Group A receives avapritinib with the IA regimen for fit patients, and Group B receives the VA regimen for those unfit. Phase II includes two treatment arm groups (IA-based RP2D vs. VA-based RP2D). Patients will be enrolled at diagnosis, within a maximum 28-day screening period, and will be assessed for eligibility for intensive therapy and therefore assigned to a treatment arm. All screening activities will be performed after the patient's informed consent form is signed.
| Arm | Type | Receives |
|---|---|---|
| Group A (FIT): Avapritinib Combined Intensive Chemotherapy in patients with newly diagnosed AML | Experimental | Drug: Group A (FIT): Avapritinib + IA regimen |
| Group B (UNFIT): Avapritinib Combined Venetoclax/Azacitidine in patients with newly diagnosed AML | Experimental | Drug: Group B (UNFIT): Avapritinib + VA regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years, both genders
- Diagnosis of acute myeloid leukemia according to WHO 2022 criteria
- Treatment-naive patients (hydroxyurea or low-dose cytarabine <0.5g cumulative dose allowed)
- Bone marrow detection of KIT mutations with concurrent t(8;21)(q22;q22.1) or RUNX1::RUNX1T1 fusion gene; or inv(16)(p13.1q22) or t(16;16)(p13.1;q22) or CBFβ::MYH11 fusion gene
- Life expectancy >12 weeks Group A: ≥18 and <65 years with ECOG 0-1; Group B: ≥65 years or ≥18 and <65 years with comorbidities (ECOG ≥2, cardiac disease, creatinine clearance 30-50ml/min, or mild hepatic impairment)
Key exclusion criteria (6 listed)
- Known hypersensitivity to KIT inhibitors, cytarabine, idarubicin, venetoclax, azacitidine or similar agents
- Concurrent use of other KIT inhibitors (dasatinib, sorafenib, gilteritinib, midostaurin)
- Intracranial hemorrhage on imaging or unresolved prior intracranial bleeding
- Active uncontrolled infection
- Significant organ dysfunction: myocardial infarction, chronic heart failure, decompensated liver dysfunction, renal failure
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 |
|---|---|---|
| Group A (FIT): Avapritinib + IA regimenAlso: Group A (Intensive chemotherapy)Cytarabine 100mg/m² days 1-7 Idarubicin 12mg/m² days 1-3 Avapritinib orally on days 8-21 (28-day cycle) | Drug | Group A (FIT): Avapritinib Combined Intensive Chemotherapy in patients with newly diagnosed AML |
| Group B (UNFIT): Avapritinib + VA regimenAlso: Group B (Non-intensive chemotherapy)Venetoclax 100mg day 1, 200mg day 2, 400mg days 3-28 Azacitidine 75mg/m² days 1-7 Avapritinib orally on days 8-21 (28-day cycle) | Drug | Group B (UNFIT): Avapritinib Combined Venetoclax/Azacitidine in patients with newly diagnosed AML |
Primary outcome
Phase I: Recommended phase 2 dose (RP2D)
Time frame: Approximately 6 months after first patient first visit (FPFV)
Recommended phase 2 dose (RP2D) of IA-based and VA-based combination with avapritinib schedules
Phase II: MRD (Measure residual disease) negativity rate
Time frame: Aproximatey 2 years after FPFV
MRD negativity rate - proportion of patients achieving ≥3-log reduction in RUNX1::RUNX1T1 or CBFβ::MYH11 fusion gene levels by qPCR between the 1st and 2nd consolidation courses.
3 secondary outcomes
Overall survival (OS)
Time frame: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
Composite complete remission rate (CRc)
Time frame: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
Adverse Event
Time frame: Through study completion: 2 years after the last patient has been enrolled into the study, an average of 48 months.
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 19 Jun 2025.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Group A (FIT): Avapritinib + IA regimen and Group B (UNFIT): Avapritinib + VA regimen in people with Acute Myeloid Leukemia With T(8;21)(Q22;Q22) and Acute Myeloid Leukemia With T(16;16)(P13;Q22), run by The First Affiliated Hospital of Soochow University 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 6 inclusion and 6 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 19 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Su-ning Chen, M.D. (008613814881746, chensuning@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Recommended phase 2 dose (RP2D) (time frame: Approximately 6 months after first patient first visit (FPFV)). The study lists 2 primary outcomes in all. 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 19 Jun 2025.