Vaccination With Autologous Dendritic Cells Loaded With Autologous Tumour Homogenate in Glioblastoma

NCT ID: NCT04523688

Last Updated: 2025-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-25

Study Completion Date

2025-12-31

Brief Summary

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Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen).

Detailed Description

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Single arm, monocentric trial to assess the safety and the progression-free survival related to the combined treatment of dendritic cell vaccine loaded with autologous tumor homogenate and temozolomide in patients operated for glioblastoma and then treated with standard radiochemotherapy (according to Stupp regimen).

The experimental treatment consists of an induction phase with 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4), followed by a maintenance phase consisting of 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments. After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.

Primary objectives are clinical activity and safety of the study treatment. Secondary objectives are the evaluation of the prognostic role of the positive Delayed-Type Hypersensitivity (DTH) skin test after at least four vaccine administrations, the OS and the immunological efficacy of the study treatment. A series of exploratory objectives will be also assessed on samples from patients who participate to this optional part of the trial.

Simon's two-stage design (Simon, 1989) will be used for the sample size calculation.

A planned interim analysis will be done after the recruitment of the first 9 evaluable patients for toxicity and for efficacy.

If study will not be stopped due to lack of safety or efficacy, a total of 28 evaluable patients will be enrolled for the trial.

Time to events (PFS and OS) will be calculated with the Kaplan-Meier method and the analysis was performed on the eligible population. For the primary objective, the proportion of patients without progression at three months from leukapheresis date will be evaluated. The proportion of patients experiencing vaccine-related grade ≥ 3 adverse events (AEs) during the treatment will be inferred by means of the two-sided Clopper-Pearson, or a more appropriate one, 95% confidence interval. Descriptive statistics will be used to assess the extent of the secondary endpoints.

Conditions

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Glioblastoma Vaccination

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental treatment

Induction phase: 4 weekly doses of dendritic cell vaccine (10x10exp6 cells) intradermally administered (weeks 1-4).

Maintenance phase: 28 days cycles with vaccine administration (start on week 7) and adjuvant temozolomide (150-200mg/m2/day) assumed orally from day 1 to 5 q28 (start on week 5). The combined maintenance treatment will continue until disease progression, unacceptable toxicity or withdrawal of consent by the patient, or up to a maximum of 1 year of treatments.

After disease progression or the end of maintenance phase, is foreseen a one-year follow-up phase for each subject.

Group Type EXPERIMENTAL

Autologous Dendritic Cells (DC) vaccine

Intervention Type BIOLOGICAL

10×10exp6 autologous dendritic cells loaded with autologous tumour homogenate given by intradermal injection (day 1)

Temozolomide

Intervention Type DRUG

Adjuvant temozolomide assumed orally from day 1 to 5 (start on week 5). Dosage: 150mg/m2/day for the first cycle and 200 mg/m2/day for subsequent cycles (q28).

Interventions

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Autologous Dendritic Cells (DC) vaccine

10×10exp6 autologous dendritic cells loaded with autologous tumour homogenate given by intradermal injection (day 1)

Intervention Type BIOLOGICAL

Temozolomide

Adjuvant temozolomide assumed orally from day 1 to 5 (start on week 5). Dosage: 150mg/m2/day for the first cycle and 200 mg/m2/day for subsequent cycles (q28).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Ridolfi, DR

Role: STUDY_CHAIR

IRST IRCCS

Locations

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Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Meldola, FC, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Oriana Nanni, DR

Role: CONTACT

+39 0543739266

Anna Miserocchi, DR

Role: CONTACT

Facility Contacts

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Laura Ridolfi, DR

Role: primary

+39 0543 739274

Other Identifiers

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IRST191.05

Identifier Type: -

Identifier Source: org_study_id

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