Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy

NCT ID: NCT03548571

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-26
• Study Completion Date: 2026-05-01

Brief Summary

Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is dendritic cells transfected with mRNA of survivin, hTERT og autologous tumor stem cells derived from tumorspheres.

Detailed Description

Autologous leukapheresis for enrichment of PBMCs is performed after enrollment of the patient into the trial. Ex vivo generated DCs will be frozen and stored in the vapour phase of liquid nitrogen.

At first surgery, tumor biopsies will be cultured under sphere-forming conditions under ex vivo conditions for enrichment of glioblastoma stem cells. mRNA will purified and amplified from these autologous tumor stem cells.

At specified intervals patients randomized to the vaccine group will receive intradermal injections of DCs transfected with mRNA from autologous tumor stem cells, survivin and hTERT. Injections will be given as three separate injections at three separate sites.

Vaccination will be continued for as long as there are vaccines available.

Conditions

Glioblastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DC immunization

Leukapheresis before start of radiotherapy. Immunization with DCs starting first week after finalizing radiotherapy (2Gy x 30) and concomitant temozolomide.

Group Type: EXPERIMENTAL

Dendritic cell immunization

Intervention Type: BIOLOGICAL

Intradermal injection

Standard therapy

Radiotherapy (2 Gy x30) with concomitant and adjuvant temozolomide.

Group Type: ACTIVE_COMPARATOR

Adjuvant temozolomide

Intervention Type: DRUG

After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days at 150 mg per square meter for the first cycle and thereafter increase to 200 mg per square meter beginning with the second cycle.

Interventions

Dendritic cell immunization

Intradermal injection

Intervention Type: BIOLOGICAL

Adjuvant temozolomide

After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days at 150 mg per square meter for the first cycle and thereafter increase to 200 mg per square meter beginning with the second cycle.

Intervention Type: DRUG

Other Intervention Names

Standard therapy

Eligibility Criteria

Inclusion Criteria

All of the following conditions must apply:

• Must be at least 18 years and less than 70 years of age.
• Must be ambulatory with a ECOG performance status 0 or 1
• Must have histologically confirmed glioblastoma IDH wild-type, with unmethylated MGMT-gene promotor, and a candidate for combined radiation therapy and chemotherapy ("Stupps Regimen").
• Must have accessible volume and quality of tumor tissue for vaccine production (proliferation of cells and extraction of tumor mRNA) at first surgery.
• Must have postoperative MRI after surgery with contrast enhancing tumor remnant of less than 1 cm3 or less than 10% of original tumor volume.
• Normal organ function defined by laboratory values as following: ANC > 1.5 x 109/L; platelets >100 x109/L, Hb >9g/dL (> 5.6 mmol/L). Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance >40 mL/min, Bilirubin < 20% above the upper limit of normal, ASAT and ALAT < 2.5 the upper limit of normal. Albumin >2.5 g/L.
• Serology indicating contagious HIV, HBV, HCV and Treponema pallidum must be negative.
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria

• Tumor in a localization where a modest increase in size due to reactive oedema may have a large impact on the patient's neurological condition, i.e. brain stem.
• History of prior malignancy other than glioblastoma, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and ca. cervicis stage IB.
• Active infection requiring antibiotic therapy.
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.
• Prior splenectomy.
• Glucocorticoid treatment not possible to terminate due to autoimmune disease or increased intracranial pressure.
• Adverse reactions to vaccines such as asthma, anaphylaxis or other serious reactions.
• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
• Chemotherapy or other potentially immune-suppressive therapy outside protocol that has been administered within the last 4 weeks prior to vaccination.
• Positive pregnancy test in women of childbearing potential (within 7 days before the first vaccination). Women of childbearing potential and sexually active male participants must use reliable methods of contraception during the whole treatment period and 3 months after the last trial drug dose. Reliable methods of contraception are defined in section .
• Any reason why, in the opinion of the investigator, the patient should not participate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Einar Vik-Mo

Senior consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Iver A Langmoen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Oslo University Hospital

Oslo, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Einar O Vik-Mo, MD, PhD

Role: CONTACT

uxvieb@ous-hf.no

+47 23074340

Soveig Bringsli

Role: CONTACT

solbri@ous-hf.no

Facility Contacts

Einar O Vik-Mo, MD, PhD

Role: primary

uxvieb@ous-hf.no

+47 23074340

Solveig Bringsli

Role: backup

solbri@ous-hf.no

References

Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tonnesen P, Suso EM, Saeboe-Larssen S, Sandberg C, Brinchmann JE, Helseth E, Rasmussen AM, Lote K, Aamdal S, Gaudernack G, Kvalheim G, Langmoen IA. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother. 2013 Sep;62(9):1499-509. doi: 10.1007/s00262-013-1453-3. Epub 2013 Jul 2.

Reference Type: RESULT

PMID: 23817721 (View on PubMed)

Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170. No abstract available.

Reference Type: DERIVED

PMID: 32691060 (View on PubMed)

Other Identifiers

DEN-STEM

Identifier Type: -

Identifier Source: org_study_id