Vaccination with personalized dendritic cells for glioblastoma treatment

Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma: a Phase II Study

This study is testing a personalized vaccine made from patients' own tumor cells, combined with a standard drug, to see if it can help people who have had surgery for glioblastoma live longer without their cancer coming back.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Meldola, FC)
• Trial ID: NCT04523688 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of a dendritic cell vaccine loaded with the patient's own tumor homogenate, combined with temozolomide, in patients who have undergone surgery for glioblastoma. Participants will receive an initial four weekly doses of the vaccine, followed by a maintenance phase that includes additional vaccine doses and oral temozolomide. The study aims to assess progression-free survival and the immunological response to the treatment. Patients will be monitored for safety and clinical activity throughout the trial and for one year after treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed monofocal glioblastoma who have undergone near-complete surgical resection.

Not a fit: Patients with multifocal glioblastoma or those who are not suitable for leukapheresis may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the immune response against glioblastoma and improve patient survival rates.

How similar studies have performed: While similar approaches using dendritic cell vaccines have shown promise in other studies, this specific combination with temozolomide is relatively novel.

Eligibility criteria

After signing the informed consent form for pre-screening, patient will assess the procedures to obtain sufficient leukapheretic material for the dendritic cell vaccine manufacturing and will perform the standard radiochemotherapy treatment (Stupp regimen) for the disease.

For the pre-screening phase of the study the eligibility criteria are:

1. Histologically confirmed "monofocal" glioblastoma
2. Near-complete resection (= 5 ml residual tumor volume) confirmed by "central neuroradiologist on magnetic resonance imaging (MRI) or CT scan within 72 h postoperative"
3. Karnofsky performance status (KPS) = 70% or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix A)
4. Be willing and able to provide written informed consent/assent for the pre-screening phase of the trial.
5. Be = 18 years of age on day of signing informed consent.
6. Life expectancy of greater than 12 weeks.
7. Patient suitable for the collection of biological material from leukapheresis:

   serological tests HIV, hepatitis B virus (HBV), HCV, Treponema pallidum negative; normal cardiological parameters (ECG and cardiological examination); evaluation by transfusionist to exclude possible contraindications to leukapheresis.
8. Patient candidate to standard radiochemotherapy (Stupp regimen)
9. Appropriate 12-lead ECG and echocardiogram.

After pre-screening, patient will be enrolled based on subsequent Inclusion Criteria:

1. Histologically confirmed "monofocal" glioblastoma
2. THE AUTOLOGOUS SURGICAL SPECIMEN NEEDED FOR VACCINE MANUFACTURING MUST HAVE BEEN COLLECTED AND SENT TO THE SOMATIC CELL THERAPY LAB OF ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (IRST) ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO (IRCCS) AND MUST FULFIL ALL THE ACCEPTANCE CRITERIA PRESCRIBED BY THE GOOD MANUFACTURING PRACTICES (GMP) PROCEDURES.
3. Availability of sufficient leukapheretic material for the preparation of the vaccine product.
4. No progressive disease near-complete resection (= 5 ml residual tumor volume) confirmed by MRI after standard radiochemotherapy treatment (Stupp regimen)
5. Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments.
6. Be willing and able to provide written informed consent/assent for the trial.
7. Be \>= 18 years of age on day of signing informed consent.
8. Have a Karnofsky performance status (KPS) = 70% or a performance status of 0 or 1 on the ECOG Performance Scale.
9. Demonstrate adequate organ and marrow function

Exclusion Criteria:

1. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy \> 10 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
2. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3. Has a known history of active Bacillus Tuberculosis (TB)
4. Previous treatment with a cancer vaccine
5. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery.
6. Any known history of or is positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous.
7. Has received a live vaccine within 30 days of planned start of study therapy.

Where this trial is running

Meldola, FC

• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) — Meldola, Fc, Italy (Recruiting)

Study contacts

• Study coordinator: Oriana Nanni, DR

Conditions Glioblastoma; Vaccination; glioblastoma; dendritic cells; vaccine; temozolomide; Stupp regimen; cellular therapy