Early phase clinical trial to evaluate the safety of the combination of immunotherapy with dendritic cells pulsed and tumor lysate, together with CAR-T cells targeting IL13Ra2, in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG)

Prior treatment

• Patients receiving other antitumor treatments. If previously treated, a washout period of at least 4 weeks is required.
• Patients requiring corticosteroid treatment at a daily dose >2 mg/day dexamethasone (or equivalent).
• Patients for whom corticosteroid treatment cannot be suspended during the week prior to leukapheresis.
• Patients receiving bevacizumab for pseudoprogression who do not show neurological stability.

Other illness

• Patients with disease progression or disseminated disease on MRI at diagnosis.
• HIV+, HCV+, HBV+ patients or those not meeting the serological screening criteria described in Annex 5.
• Patients with uncontrolled infections.

Other

• Pregnancy.
• Breastfeeding.
• Participation in another experimental study within the last 3 months.
• Associated comorbidities that, in the investigator’s clinical judgement, cannot be adequately controlled and may compromise the patient’s ability to tolerate the study treatment.
• Patients with neoplasms other than DIPG.

• Written informed consent signed by the patient or legal representative and, if applicable, informed assent (for minors aged ≥12 years).
• Candidates for placement of an Ommaya reservoir with intraventricular catheter.
• Fertile males and females must use a highly effective contraceptive method.
• Newly diagnosed DIPG based on clinical-radiological criteria and/or histological and molecular confirmation. Biopsied patients must show K27M mutation. Clinical and radiological criteria will be assessed by the PI with support from a neuroradiologist at Hospital Sant Joan de Déu.
• Prior neoadjuvant radiotherapy (standard of care for DIPG) before receiving the trial treatment. Radiotherapy defined as 54–60 Gy in 1.8–2.2 Gy/fraction.
• Age between 3 and 24 years inclusive.
• Lansky performance score ≥50%. For patients ≥16 years, Karnofsky score ≥50%.
• Life expectancy greater than 12 weeks.
• Preserved bone marrow function: absolute neutrophil count >1,000/mcL, platelets >100,000/mcL (independent of transfusions), haemoglobin >8 g/dL (may be transfusion-dependent).
• Normal liver and kidney function, defined as: Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) for age, unless the patient has Gilbert syndrome. ALT or AST < 2.5 times the ULN for age. Creatinine < 1.5 times the ULN.
• Adequate venous access for leukapheresis.