Critères d'inclusion : 1. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines
2. Age at inclusion: 3 to <18 years of age
3. Patients should be able and willing to comply with study visits and procedures as per protocol.
4. Patients must be affiliated to a social security system or beneficiary of the same according to local requirements
5. Sexually actice females of childbearing potential must have a negative serum pregnancy test within 24 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 5 months after the last study treatment administration. Sexually active males patients (and their female partner) must agree to use condom during the study and for at least 7 months after the last study treatment administration. Acceptable contraception is listed in Appendix 7.
6. Newly diagnosed non-brainstem WHO grade III and IV HGG and neuroglial tumors; gliomatosis cerebri or diffuse glioma, metastatic malignant glial tumors, multifocal gliomas and bithalamic gliomas are eligible for the study. Diffuse midline gliomas with H3K27M mutation are not eligible. Anaplastic ganglioglioma and anaplastic pleïomorphic astrocytoma will be eligible.
7. Local histological diagnosis has been confirmed centrally by a designated reference pathologist.
8. Able to commence trial treatment within 6 weeks following the last major surgery.
9. Adequate Bone Marrow Function : Hemoglobin 10 g/dL (transfusion independent), Neutrophil count 1.0 109/L. Platelet count 100 109/L (transfusion independent)
10. Absence of Coagulation Disorder
11. Adequate Liver Function : AST 2.5x institutional ULN for age, ALT 2.5x institutional ULN for age, Total Bilirubin 1.5x institutional ULN for age
12. Adequate Renal Function : Serum creatinine must be 1.5x ULN for age, absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of 2
Critères de non-inclusion : 1. Any disease or condition that contraindicates the use of the study medication/treatment (for TMZ, see the approved product labelling) or places the patient at an unacceptable risk of experiencing treatment related complications.
2. Patients should not be on high-dose steroids (ie > 1mg/kg) before study entry; doses should be stable for at least two weeks or decreasing.
3. Low probability of protocol compliance.
4. Radiological evidence of surgically related intracranial bleeding (excluding asymptomatic, resolving hemorrhagic changes associated with recent surgery and the presence of punctuate hemorrhage in the tumor).
5. Subjects with concommitant second malignanices are excluded unless a complete remission is achieved as it is empirically determined based on the malignancy and treatment provided prior to study entry and no additional therapy is required or anticipated to be required during the study period.
6. Previous cranial irradiation.
7. Any known auto-immune disease, previous or ongoing.
8. Known chronic inflammatory digestive disease, previous or ongoing.
9. Chronic asthma receiving corticotherapy, even only with inhalation.
10. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of study drug
11. Pregnant or breastfeeding women
12. Known hypersensitivity to any component of the products (study drug or ingredients)
13. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).
14. Patients who are currently receiving another investigational drug or anticancer agent
15. Patient who have an uncontrolled infection
16. Patient with known human immunodeficiency virus (HIV) / AIDS infection or acute / chronic Hepatitis B or C