Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

NCT06221683 | Recruiting Phase 2 DMC

• 1 other identifier: GMCAII
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 13

Brief Summary

The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.

Conditions

AML, Childhood; Acute Myeloid Leukemia

Keywords

AML; Childhood; Molecular subtyping; MRD

Outcome Measures

Primary Outcomes (3)

• Rate of CR/CRi with negative MRD

  CR/CRi with negative MRD was defined as less than 5% blasts in bone marrow and MRD \<0.1%.

  Day 26 (HAE group) and Day 32 (MAG+Ven group) for remission induction 1 and 2 are the necessary time points for response evaluation.

• Event-free survival

  Events/failures of EFS include any-cause death, relapse, second malignancy, no CR after Indiction II and off-therapy due to abandonment or attending physician's decision. Induction II and off-therapy due to abandonment or attending physician's decision.

  From date of treatment until the date of the occurrence of the event, whichever comes first, assessed up to 72 months. Patients remaining event-free are censored at the last follow-up time.

• Cumulative incidence of relapse

  Failures of CIR only include relapse and no CR after Induction 2. Other failures including death in resission (before repalse), second malignancy, and off-therapy due to abandonment or attending physician's decision are considered competing risk.

  From date of treatment until the date of when a failure of CIR occurs, whichever comes first, assessed up to 72 months.

Study Arms (2)

SDC group

EXPERIMENTAL

Patients with CBF fusion gene (RUNX1: : RUNX1T1 and CBFB: : MYH11) or KMT2A: : MLLT3(AF9) , KMT2A: : MLLT10(AF10) , KMT2A: : MLLT4(AF6) fusion gene or KIT mutation will receive SDC regimen, including one course of HAE (Homoharringtonine, cytarabine, etoposide) in induction I. These patients will continue on the SDC (HAE) regimen in the second course if the MRD is \< 1% after induction I, otherwise venetoclax will be added to the SDC group sequentially on Day 2 after the end of HAE. FLT3-ITD will be given sorafenib or gilteritinib as early as possible, and patients with KIT mutations will be recommended to add avapritinib as appropriate. These targeted drugs will not be combined with venetoclax.

Drug: Homoharringtonine; Drug: Cytarabine; Drug: Etoposide; Drug: Venetoclax; Drug: Sorafenib; Drug: Gilteritinib; Drug: Avapritinib

LDC group

EXPERIMENTAL

Patients with the exception of the CBF fusion gene (RUNX1: : RUNX1T1 and CBFB: : MYH11) or those with the KMT2A: : MLLT3(AF9) , KMT2A: : MLLT10(AF10) , KMT2A: : MLLT4(AF6) fusion gene or KIT mutation will receive the LDC (MAG/IDAG+ venetoclax) regimen in induction I. Patients with MRD ≥1% or KIT mutations, assessed after induction I, will receive the HAE plus venetoclax (or targeted drugs) regimen, otherwise, they will receive MAG/IDAG + venetoclax. FLT3-ITD will be given sorafenib or gilteritinib as early as possible, and patients with KIT mutations will be recommended to add avapritinib as appropriate. These targeted drugs will not be combined with venetoclax.

Drug: Cytarabine; Drug: Mitoxantrone hydrochloride liposome; Drug: Recombinant Human Granulocyte Colony-Stimulating Factor; Drug: Idarubicin Hydrochloride; Drug: Sorafenib; Drug: Gilteritinib; Drug: Avapritinib

Interventions

Homoharringtonine DRUG

3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤10kg, d1-7, ivgtt, qd, more than 6 hours

Also known as: Homoharringtonine injection

SDC group

Cytarabine DRUG

100mg/m2/q12h for weighing \>10kg, 3.3mg/kg/q12h for weighing ≤10kg, d1-7, ivgtt, q12h, more than 30 minutes in SDC group; 10mg/m2/q12h for weighing \>10kg, 0.33mg/kg/q12h for weighing ≤10kg, d1-10, s.c.,q12h (the first dose at 8 am) in the LDC group;

Also known as: Cytosar

LDC group; SDC group

Etoposide DRUG

100mg/m2/d for weighing \>10kg, 3.3mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 4 hours

Also known as: Etoposide injection

SDC group

Venetoclax DRUG

100mg/m2/d for weighing \>10kg, 3.33mg/kg/d for weighing ≤10kg, d12-25, po, qd

Also known as: Venclexta

SDC group

Mitoxantrone hydrochloride liposome DRUG

5mg/m2/d for weighing \>10kg, 0.17mg/kg/d for weighing ≤ 10kg, d1, 3, 5, ivgtt, qod, more than 2 hours at 10 am.

Also known as: Mitoxantrone hydrochloride liposome injection

LDC group

Recombinant Human Granulocyte Colony-Stimulating Factor DRUG

5ug/kg/d, d1-10, s.c., qd, at 1pm

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

LDC group

Idarubicin Hydrochloride DRUG

3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 6 hours.

Also known as: Idarubicin hydrochloride injection

LDC group

Sorafenib DRUG

100mg/m2/day for weighing \>10kg, 3.3mg/kg/day for weighing ≤10kg, from identification, po, qd

Also known as: Nexavar

LDC group; SDC group

Gilteritinib DRUG

20mg/m2/day for weighing \>10kg, 0.7mg/kg/day for weighing ≤ 10kg, from identification, po, qd

Also known as: Xospata Pill

LDC group; SDC group

Avapritinib DRUG

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

Also known as: AYVAKIT

LDC group; SDC group

Eligibility Criteria

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

You may qualify if:

• 、Newly diagnosed, untreated AML；
• 、Under 18 years old;
• 、Patients who have used hydroxyurea or cytarabine before diagnosis, but the dosage of cytarabine does not exceed 5 days, and the total dose does not exceed 500 mg/m2 (50 mg/m2, q12h × 5d)；
• 、 Liver function：Tbil≤2×ULN, ALT/AST≤3×ULN, creatinine clearance ≥50ml/min；Cardiac NYHA grading\<3；SaO2\>92%;
• 、No active infection (symptoms resolved for more than 3 days if infected)
• 、ECOG\<2;
• 、Expected survival time greater than 12 weeks;
• 、Obtain the consent of the child and/or guardian and sign the informed consent form.

You may not qualify if:

• 、Acute megakaryocytic leukemia (AMKL)；
• 、Acute promyelocytic leukemia (APL);
• 、Treatment-related secondary AML and AML with definite MDS transformation；
• 、Myeloproliferative neoplasm (such as Juvenile myelomonocytic leukemia, JMML);
• 、AML secondary to congenital bone marrow failure (such as AML secondary to Fanconi anemia (FA)；
• 、AML secondary to Down syndrome;
• 、Only temporary chemotherapy, radiotherapy, or immunotherapy, but not systematic treatment according to the treatment plan;
• 、 Temporary chemotherapy, radiotherapy, or immunotherapy only, not systemic therapy per protocol;
• 、Patients with very poor nutritional status, severe infection, cardiac insufficiency, and intolerance to chemotherapy;
• 、Relapsed AML at any time；
• 、The attending physician considers that the patient is not suitable for entering the study protocol based on the patient's physical condition, economic status, and other factors.

Sponsors & Collaborators

• Children's Hospital of Soochow University: lead

Study Sites (13)

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

Beijing Institute of Genomics, Chinese Academy of Sciences

Beijing, 100000, China

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Homoharringtonine; Cytarabine; Etoposide; venetoclax; Idarubicin; Sorafenib; gilteritinib; avapritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Shaoyan Hu, MD, PhD

  Children 's Hospital of Soochow University

  STUDY CHAIR

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 24, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (13)