AML, ChildhoodPhase 2NCT06316960
Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation
A Phase 2 study testing Avapritinib, Azacitidine Injection and Decitabine Injection in people with AML, Childhood and Relapse/Recurrence, run by Children's Hospital of Soochow University at 12 sites in China.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- AML, Childhood, Relapse/Recurrence, Refractory AML
- What is being tested?
- Avapritinib, Azacitidine Injection and Decitabine Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 12 sitesChina
- Study dates
- 1 Mar 2024to Mar 2027
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Gender unlimited;
- Under 18 years;
- Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification).
- Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFβ::MYH11;
- KIT mutation;
- Refractory AML: AML patients who do not achieve CR or CRi after induction therapy;
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- Relapsed AML: patients who achieved remission after consolidation therapy or transplantation, FISH confirmed that the fusion gene turned positive, or extramedullary leukemia infiltration;
- No active infections;
- Liver function: Tbil ≤2×ULN, ALT/AST ≤3×ULN, creatinine clearance ≥50ml/min;
- ECOG score <2;
- Expected survival time >12 weeks;
- Participants must have the ability to understand and be willing to participate in this study and must sign an informed consent form.
Who cannot join
- Have received prior treatment with avapritinib;
- Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc;
- Presence of active uncontrolled infection (including bacterial, fungal, or viral infection);
- Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction；
- With other malignancies requiring treatment；
- Already enrolled in another interventional clinical study；
- The researchers determined that the individual is not suitable to participate in this trial.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
China12 sites, 12 recruiting
- Not yet recruiting
Third Xiangya Hospital of Central South University
Changsha, Hunan, 410000
Minghua Yang, MD, +86-13973135843, yamahua123@163.com
- Not yet recruiting
XiangYa Hospital Central South University
Changsha, Hunan, 410008
Liangchun Yang, MD,PhD, +86-13974927514, yangliangchung@163.com
- Not yet recruiting
Guangzhou Women and Children Medical Center
Guangzhou, Guangdong, 510000
Hua Jiang, MD, PhD, +86-13533330985, jiang_hua18@sina.cn
- Not yet recruiting
First Affiliated Hospital Of University of Science and Technology of China
Hefei, Anhui, 230000
Chun Li, MD,PhD, +86-13865992676, lichun1230@sohu.com
- Not yet recruiting
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230000
Ninglin Wang, MD, +86-13721113063, zwnltt@126.com
- Not yet recruiting
Qilu Hospital of Shandong University
Jinan, Shandong, 250000
Xiuli Ju, MD,PhD, +86-13869192944, shellysdcn@hotmail.com
- Not yet recruiting
Kaifeng Children's Hospital
Kaifeng, Henan, 475000
Jixia Luo, MD, +86-13592146539, luojixia@163.com
- Not yet recruiting
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530000
Ning Liao, MD, +86-13978812808, ln12808@163.com
- Not yet recruiting
Children's Hospital Of Fudan University
Shanghai, Shanghai Municipality, 200000
Xiaowen Zhai, MD, PhD, +86-18017590808, zhaixiaowendy@163.com
- Recruiting
Children's Hospital of Soochow University
Suzhou, Jiangsu, 215000
Shaoyan Hu, MD, PhD, +86-13771835430, hsy139@126.com
Li Gao, MD, +86-15821963190, joygaoli@163.com
- Not yet recruiting
Xuzhou Children's Hospital
Xuzhou, Jiangsu, 221000
Qi An, MD, +86-13814422329, anqi1974@sina.com
- Not yet recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052
Yufeng Liu, MD,PhD, +86-13673666608, lyf6012@126.com
About this study
Official title: A Prospective, Multicenter Clinical Study on The Safety and Efficacy of Avapritinib in The Treatment of Relapsed/Refractory Pediatric Core Binding Factor Acute Myeloid Leukemia (CBF-AML) With KIT Mutation
The purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation.
Read the detailed description
This is a multicenter, single-arm, prospective, and intervention trial. About 30% of core binding factor acute myeloid leukemia (CBF-AML) patients still relapse under current treatment. Some studies have found that KIT mutations, especially the D816V mutation, may predict relapse and decrease overall survival (OS) in CBF-AML. Avapritinib has been approved for the treatment of gastrointestinal stromal tumors with KIT or PDGFRA mutations. Avapritinib was also effective for the treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and KIT mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation in a single-center, retrospective report. 11 centers from China carry out the AVACBFKIT regimen including Avapritinib, hypomethylating agents and low dose chemotherapy for the treatment of relapsed or refractory pediatric CBF-AML with KIT mutation. The main focus of this study is to evaluate the efficacy and safety of avapritinib in the regimen.
- Conditions
- AML, Childhood, Relapse/Recurrence, Refractory AML, Core Binding Factor Acute Myeloid Leukemia, C-KIT Mutation
- Being tested
- Avapritinib, Azacitidine Injection, Decitabine Injection, Idarubicin Hydrochloride, Cytarabine
- Keywords
- Avapritinib, KIT, CBF AML, Childhood, Relapsed/Refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvapritinibDrug
Also called AYVAKIT
50mg/m2/day for weighing bodyweight >10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.
Azacitidine InjectionDrug
Also called Azacitidine
75mg/m2/d for weighing >10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
Decitabine InjectionDrug
Also called Decitabine
20mg/m2/d for weighing >10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
Idarubicin HydrochlorideDrug
Also called Idarubicine
5mg/m2/day for weighing >10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am.
CytarabineDrug
Also called CYTOSAR
10mg/m2/day for weighing >10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.
Granulocyte Colony-Stimulating FactorDrug
Also called Recombinant Human Granulocyte Colony-Stimulating Factor Injection
300ug/day for weighing >10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.
| Study group | Role | What they receive |
|---|---|---|
| Relapsed/Refractory CBF-AML with KIT mutation | Experimental | The relapsed/refractory patients will receive a combination treatment of decitabine/azacitidine+ IdAG (idarubicine + cytarabine + granulocyte stimulating factor)regimen along with avapritinib. CBF-AML with KIT mutated patients with molecular relapse after hematopoietic stem cell transplantation may receive avapritinib combined with demethylating agents or interferon or donor lymphocyte infusion without low-dose chemotherapy. The dose of avapritinib will start at 50mg/m2/d, and if platelets stabilize at 50 ×10^9/L and neutrophils stabilize above 1.0 ×10^9/L after one week, the dose can be increased to 100mg/m2/d, with a maximum daily dose of 100mg. Avapritinib should be discontinued in the presence of febrile neutropenia or active infection, and avapritinib can be resumed once the infection is controlled, with each treatment cycle not exceeding 28 days. Receives: Drug: Avapritinib; Drug: Azacitidine Injection; Drug: Decitabine Injection; Drug: Idarubicin Hydrochloride; Drug: Cytarabine; Drug: Granulocyte Colony-Stimulating Factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite remission rate (CRc)
Composite remission rate (CRc), including the sum of the number of patients with complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), and morphologically leukemia-free (MLFS) as a percentage of the total number of patients who participated in the efficacy analysis.
Measured: The evaluation time point is day28-day35 from the start of regimen.
Secondary outcomes (2)
Overall survival
Overall survival (OS) was defined as the date from enrollment to the date of death or last follow-up for surviving patients.
Measured: From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
Progression-free survival
Progression-free survival (PFS) was defined as the date from enrollment to the date of disease progression, confirmed relapse, or death, whichever occurred first.
Measured: From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2024
- Study start1 Mar 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML, ChildhoodStudies 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Soochow University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shaoyan Hu, Children's Hospital of Soochow University
- Investigators
- Shaoyan Hu, MD, PhD, Principal investigator, Children 's Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06316960
- Sponsor's protocol ID
- AVACBFKIT
- Status last verified
- Aug 2024
- First submitted
- 12 Mar 2024
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter Clinical Study on The Safety and Efficacy of Avapritinib in The Treatment of Relapsed/Refractory Pediatric Core Binding Factor Acute Myeloid Leukemia (CBF-AML) With KIT Mutation
- ClinicalTrials.gov ID
- NCT06316960
- Acronym / sponsor ID
- AVACBFKIT
- Conditions
- AML, Childhood, Relapse/Recurrence, Refractory AML, Core Binding Factor Acute Myeloid Leukemia, C-KIT Mutation
- Keywords
- Avapritinib, KIT, CBF AML, Childhood, Relapsed/Refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Children's Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 19 Mar 2024 (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 purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation.
Detailed description
This is a multicenter, single-arm, prospective, and intervention trial. About 30% of core binding factor acute myeloid leukemia (CBF-AML) patients still relapse under current treatment. Some studies have found that KIT mutations, especially the D816V mutation, may predict relapse and decrease overall survival (OS) in CBF-AML. Avapritinib has been approved for the treatment of gastrointestinal stromal tumors with KIT or PDGFRA mutations. Avapritinib was also effective for the treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and KIT mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation in a single-center, retrospective report. 11 centers from China carry out the AVACBFKIT regimen including Avapritinib, hypomethylating agents and low dose chemotherapy for the treatment of relapsed or refractory pediatric CBF-AML with KIT mutation. The main focus of this study is to evaluate the efficacy and safety of avapritinib in the regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Relapsed/Refractory CBF-AML with KIT mutation | Experimental | Drug: Avapritinib, Drug: Azacitidine Injection, Drug: Decitabine Injection, Drug: Idarubicin Hydrochloride, Drug: Cytarabine, Drug: Granulocyte Colony-Stimulating FactorThe relapsed/refractory patients will receive a combination treatment of decitabine/azacitidine+ IdAG (idarubicine + cytarabine + granulocyte stimulating factor)regimen along with avapritinib. CBF-AML with KIT mutated patients with molecular relapse after hematopoietic stem cell transplantation may receive avapritinib combined with demethylating agents or interferon or donor lymphocyte infusion without low-dose chemotherapy. The dose of avapritinib will start at 50mg/m2/d, and if platelets stabilize at 50 ×10^9/L and neutrophils stabilize above 1.0 ×10^9/L after one week, the dose can be increased to 100mg/m2/d, with a maximum daily dose of 100mg. Avapritinib should be discontinued in the presence of febrile neutropenia or active infection, and avapritinib can be resumed once the infection is controlled, with each treatment cycle not exceeding 28 days. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Gender unlimited;
- Under 18 years;
- Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification).
- Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFβ::MYH11;
- KIT mutation;
Key exclusion criteria (7 listed)
- Have received prior treatment with avapritinib;
- Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc;
- Presence of active uncontrolled infection (including bacterial, fungal, or viral infection);
- Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction；
- With other malignancies requiring treatment；
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 |
|---|---|---|
| AvapritinibAlso: AYVAKIT50mg/m2/day for weighing bodyweight >10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
| Azacitidine InjectionAlso: Azacitidine75mg/m2/d for weighing >10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
| Decitabine InjectionAlso: Decitabine20mg/m2/d for weighing >10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
| Idarubicin HydrochlorideAlso: Idarubicine5mg/m2/day for weighing >10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
| CytarabineAlso: CYTOSAR10mg/m2/day for weighing >10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
| Granulocyte Colony-Stimulating FactorAlso: Recombinant Human Granulocyte Colony-Stimulating Factor Injection300ug/day for weighing >10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd. | Drug | Relapsed/Refractory CBF-AML with KIT mutation |
Primary outcome
Composite remission rate (CRc)
Time frame: The evaluation time point is day28-day35 from the start of regimen.
Composite remission rate (CRc), including the sum of the number of patients with complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), and morphologically leukemia-free (MLFS) as a percentage of the total number of patients who participated in the efficacy analysis.
2 secondary outcomes
Overall survival
Time frame: From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
Progression-free survival
Time frame: From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 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 22 Aug 2024.
- 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.
Shaoyan Hu, MD, PhD principal investigator
Children 's Hospital of Soochow University
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avapritinib, Azacitidine Injection and Decitabine Injection in people with AML, Childhood and Relapse/Recurrence, run by Children's Hospital of Soochow University at 12 sites 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 12 inclusion and 7 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 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites 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 Shaoyan Hu, MD, PhD (+86-13771870462, hsy139@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite remission rate (CRc) (time frame: The evaluation time point is day28-day35 from the start of regimen.). 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 22 Aug 2024.