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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Sant Joan De Deu

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-12-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Instituto de Salud Carlos III

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the safety of the first-in-human administration of a combination of dendritic cell (DC) immunisation (DIPG-DC) pulsed with lysates derived from a pool of 8 DIPG K27M-positive tumour cell lines (DIPG-lysate), together with intraventricular administration of anti-IL13Ra2 CAR-T cells (ARI0008), derived from T cells previously stimulated by DCs, in a cohort of patients with DIPG.

Secondary objectives 8

1. To assess the tolerability of the treatment.
2. To evaluate the feasibility of the combination therapy proposed in the study.
3. To assess the non-specific and anti-tumour immunogenic response generated in peripheral blood and cerebrospinal fluid (CSF) following administration of the proposed regimen.
4. Initial evaluation of the efficacy of the complete treatment through analysis of its impact on overall survival (OS) and progression-free survival (PFS) during the disease course.
5. To monitor tumour burden evolution in CSF by detecting the K27M mutation as the treatment regimen progresses.
6. To evaluate the pharmacokinetics of the CAR-T product.
7. To identify potential factors (neuroradiological, baseline tumour burden, histological and molecular characterisation) that may influence clinical progression and/or immunological response in peripheral blood and CSF.
8. To describe the quality of life (QoL) of patients enrolled in the study.

Conditions and MedDRA coding

Patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Written informed consent signed by the patient or legal representative and, if applicable, informed assent (for minors aged ≥12 years).
2. 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.
3. 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.
4. Age between 3 and 24 years inclusive.
5. Lansky performance score ≥50%. For patients ≥16 years, Karnofsky score ≥50%.
6. Life expectancy greater than 12 weeks.
7. 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).
8. Normal liver and kidney function.
9. Adequate venous access for leukapheresis.
10. Candidates for placement of an Ommaya reservoir with intraventricular catheter.
11. Fertile males and females must use a highly effective contraceptive method.

Exclusion criteria 12

1. Patients with disease progression or disseminated disease on MRI at diagnosis.
2. Participation in another experimental study within the last 3 months.
3. Patients receiving other antitumor treatments. If previously treated, a washout period of at least 4 weeks is required.
4. 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.
5. Patients with neoplasms other than DIPG.
6. Patients requiring corticosteroid treatment at a daily dose >2 mg/day dexamethasone (or equivalent).
7. Patients for whom corticosteroid treatment cannot be suspended during the week prior to leukapheresis.
8. Patients receiving bevacizumab for pseudoprogression who do not show neurological stability.
9. Patients with uncontrolled infections.
10. HIV+, HCV+, HBV+ patients or those not meeting the serological screening criteria described in Annex 5.
11. Pregnancy.
12. Breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of Grade 3–4 serious adverse events (SAEs) according to Common Toxicity Criteria (CTC) from the start of treatment (first administration of DCs) until the end of the study per patient.

Secondary endpoints 9

1. Proportion of patients with adverse events (AEs) and serious adverse events (SAEs), as well as the proportion of patients who discontinue treatment due to AEs.
2. Percentage of patients receiving the full treatment regimen, defined as the complete administration of both DCs and CAR-T cells.
3. Evaluation of immunological parameters according to the study schedule.
4. Overall survival (OS) and progression-free survival (PFS) in DIPG patients treated with the proposed regimen. A comparison will be made with historical controls from the institution (HSJD) and other international institutions (COG and SIOP).
5. Evaluation of radiological changes following RAPNO criteria (see Annex 3: Criteria for Radiological and Clinical Response Assessment).
6. Evaluation of the distribution of anti-IL13Ra2 CAR-T cells in CSF, peripheral blood, and, if available, tumour samples, according to the study schedule.
7. Correlation between histological and molecular characterisation, clinical-radiological response, and cellular response generated in peripheral blood and CSF following treatment.
8. Correlation between immunological response and clinical progression. Determination of whether cellular response in peripheral blood and CSF correlates with increased overall survival and progression-free survival.
9. Evaluation of performance (QoL) as an indicator of quality of life. QoL will be assessed through prospective evaluation of each patient’s functionality using the PedsQL questionnaire (see Annex 2: Neurological and Functional Assessment).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Sant Joan De Deu

Sponsor organisation

Fundacio Sant Joan De Deu

Address

Calle Santa Rosa 39-57 3a Planta

City

Esplugues De Llobregat

Postcode

08950

Country

Spain

Scientific contact point

Organisation

Fundacio Sant Joan De Deu

Contact name

Andrés Morales La Madrid

Public contact point

Organisation

Fundacio Sant Joan De Deu

Contact name

Clinical Trial Unit

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications