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

NCT06316960 | Recruiting Phase 2 DMC

• 1 other identifier: AVACBFKIT
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

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

Keywords

Avapritinib; KIT; CBF AML; Childhood; Relapsed/Refractory

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall survival

  From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months.

• Progression-free survival

  From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months.

Study Arms (1)

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.

Drug: Avapritinib; Drug: Azacitidine Injection; Drug: Decitabine Injection; Drug: Idarubicin Hydrochloride; Drug: Cytarabine; Drug: Granulocyte Colony-Stimulating Factor

Interventions

Avapritinib DRUG

50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.

Also known as: AYVAKIT

Relapsed/Refractory CBF-AML with KIT mutation

Azacitidine Injection DRUG

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.

Also known as: Azacitidine

Relapsed/Refractory CBF-AML with KIT mutation

Decitabine Injection DRUG

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.

Also known as: Decitabine

Relapsed/Refractory CBF-AML with KIT mutation

Idarubicin Hydrochloride DRUG

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.

Also known as: Idarubicine

Relapsed/Refractory CBF-AML with KIT mutation

Cytarabine DRUG

10mg/m2/day for weighing \>10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.

Also known as: CYTOSAR

Relapsed/Refractory CBF-AML with KIT mutation

Granulocyte Colony-Stimulating Factor DRUG

300ug/day for weighing \>10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.

Also known as: Recombinant Human Granulocyte Colony-Stimulating Factor Injection

Relapsed/Refractory CBF-AML with KIT mutation

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Soochow University: lead

Study Sites (12)

First Affiliated Hospital Of University of Science and Technology of China

Hefei, Anhui, 230000, China

NOT YET RECRUITING

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230000, China

NOT YET RECRUITING

Guangzhou Women and Children Medical Center

Guangzhou, Guangdong, 510000, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

NOT YET RECRUITING

Kaifeng Children's Hospital

Kaifeng, Henan, 475000, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Third Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

NOT YET RECRUITING

XiangYa Hospital Central South University

Changsha, Hunan, 410008, China

NOT YET RECRUITING

Children's Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

RECRUITING

Xuzhou Children's Hospital

Xuzhou, Jiangsu, 221000, China

NOT YET RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250000, China

NOT YET RECRUITING

Children's Hospital Of Fudan University

Shanghai, Shanghai Municipality, 200000, China

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

avapritinib; Azacitidine; Decitabine; Idarubicin; Cytarabine; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Shaoyan Hu, MD, PhD

  Children 's Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shaoyan Hu, MD, PhD

CONTACT

+86-13771870462; hsy139@126.com

Li Gao, MD

CONTACT

+86-15821963190; joygaoli@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 19, 2024
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)