Vaccination with Autologous Dendritic cells loaded with Autologous Tumour homogenate in Glioblastoma: a phase II Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Mar 2021 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512493-98-00

EudraCT number

2020-003755-15

ClinicalTrials.gov

NCT04523688

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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).

Secondary objectives 3

1. Immune response in vivo
2. Clinical Outcome
3. Immunological efficacy

Conditions and MedDRA coding

Glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically confirmed glioblastoma
2. Patients must have recovered (grade 1 or less by CTCAE 5.0) from all the events related to previous treatments
3. The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of IRST IRCCS and must fulfil all the acceptance criteria prescribed by the GMP procedures
4. Availability of sufficient leukapheretic material for the preparation of the vaccine product
5. Karnofsky performance status (KPS) ≥ 70% or performance status of 0 or 1 on the ECOG Performance Scale
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. Life expectancy greater than 12 weeks
9. Patients must have normal organ and marrow function
10. Female participants of child bearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 4 months thereafter.

Exclusion criteria 17

1. Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
2. Patient with a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 20 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
3. Medical history of severe acute or chronic disease with poor prognosis, autoimmune disorder, immunodeficiency or organ allograft
4. Known history of active TB (Bacillus Tuberculosis)
5. Previous treatment with a cancer vaccine.
6. Known allergy or intolerability to components of vaccine, to TMZ
7. Severe myelosuppression
8. History of bleeding diathesis or coagulopathy
9. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status equivocal
10. 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
11. 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
12. Has known history of, or any evidence of active, non-infectious pneumonitis or interstitial lung disease
13. Has an active infection requiring systemic therapy
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
16. 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. The sole positivity for antibodies against the HBsAg (i.e. with all other HBV markers negative) is indicative of previous HBV vaccination and therefore is acceptable
17. Has received a live vaccine within 30 days of planned start of study therapy. (Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression free survival (PFS), measured as the proportion of patients without progression of disease at three months from leukapheresis
2. Proportion of patients experienced grade 3 or higher adverse events related to the study treatment

Secondary endpoints 3

1. Evaluation of the prognostic role of a positive DTH test after at least four vaccine administrations
2. Overall survival (OS)
3. Ability to enhance the proportion of circulating immune effectors specific for tumor antigens; evaluation of the persistence of an anti-tumor immune response; determination of plasma levels of a panel of inflammatory cytokines and proangiogenic factors; evaluation of the prognostic and predictive role of tumor antigen expression in tumor tissue; analysis of the prognostic and predictive role of immune cells in the peripheral blood and in the tumor microenvironment

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Sponsor organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Laura Ridolfi

Public contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

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