Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation

Relapse/Recurrence Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06316960
• Other study ID #: AVACBFKIT
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2024
• Est. completion date: March 2027

Study information

• Verified date: March 2024
• Source: Children's Hospital of Soochow University
• Contact: Shaoyan Hu, MD, PhD
• Phone: +86-13771870462
• Email: hsy139[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

1. Gender unlimited;

2. Under 18 years;

3. Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification).

4. Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFß::MYH11;

5. KIT mutation;

6. Refractory AML: AML patients who do not achieve CR or CRi after induction therapy;

7. Relapsed AML: patients who achieved remission after consolidation therapy or transplantation, FISH confirmed that the fusion gene turned positive, or extramedullary leukemia infiltration;

8. No active infections;

9. Liver function: Tbil =2×ULN, ALT/AST =3×ULN, creatinine clearance =50ml/min;

10. ECOG score <2;

11. Expected survival time >12 weeks;

12. Participants must have the ability to understand and be willing to participate in this study and must sign an informed consent form.

Exclusion Criteria:

1. Have received prior treatment with avapritinib;

2. Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc;

3. Presence of active uncontrolled infection (including bacterial, fungal, or viral infection);

4. Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction;

5. With other malignancies requiring treatment;

6. Already enrolled in another interventional clinical study;

7. The researchers determined that the individual is not suitable to participate in this trial.

Related Conditions & MeSH terms

• AML, Childhood
• C-KIT Mutation
• Core Binding Factor Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrence
• Refractory AML
• Relapse/Recurrence

Intervention

Drug:
• Avapritinib
50mg/m2/day for weighing bodyweight >10kg, 1.65mg/kg/day for weighing = 10kg, po, qd, d1-28.
• Azacitidine Injection
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 Injection
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 Hydrochloride
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.
• Cytarabine
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 Factor
300ug/day for weighing >10kg, 10ug/kg/day for weighing =10kg, d0-5, s.c., qd.

Locations

Country	Name	City	State
China	Third Xiangya Hospital of Central South University	Changsha	Hunan
China	XiangYa Hospital Central South University	Changsha	Hunan
China	Guangzhou Women and Children Medical Center	Guangzhou	Guangdong
China	First Affiliated Hospital Of University of Science and Technology of China	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Kaifeng Children's Hospital	Kaifeng	Henan
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Children's Hospital Of Fudan University	Shanghai	Shanghai
China	Children's Hospital of Soochow University	Suzhou	Jiangsu
China	Xuzhou Children's Hospital	Xuzhou	Jiangsu
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	The evaluation time point is day28-day35 from the start of regimen.
Secondary	Overall survival	Overall survival (OS) was de?ned as the date from enrollment to the date of death or last follow-up for surviving patients.	From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.
Secondary	Progression-free survival	Progression-free survival (PFS) was de?ned as the date from enrollment to the date of disease progression, con?rmed relapse, or death, whichever occurred ?rst.	From date of enrollment until the date of disease progression, con?rmed relapse, or death, whichever occurred ?rst, assessed up to 60 months.