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

NCT03548571 | Recruiting Phase 2 DMC

• 1 other identifier: DEN-STEM
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Defined as time from first surgery to first certain progress of contrast enhancing tumor or clinical progression, according to the Response Assessment in Neuro-Oncology (RANO) criteria.

  2 years

Secondary Outcomes (6)

• Overall survival

  2 years from inclusion

• Patient reported quality of life, overall

  2 years from inclusion

• Patient reported quality of life, brain specific

  2 years from inclusion

• Immunological response, skin

  2 years from inclusion

• Immunological response, cellular

  2 years from inclusion

Study Arms (2)

DC immunization

EXPERIMENTAL

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

Biological: Dendritic cell immunization

Standard therapy

ACTIVE COMPARATOR

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

Drug: Adjuvant temozolomide

Interventions

Dendritic cell immunization BIOLOGICAL

Intradermal injection

DC immunization

Adjuvant temozolomide 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.

Also known as: Standard therapy

Standard therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, Norway

RECRUITING

Related Publications (2)

• 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.

  PMID: 23817721 RESULT

• 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.

  PMID: 32691060 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Iver A Langmoen, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Einar O Vik-Mo, MD, PhD

CONTACT

+47 23074340; uxvieb@ous-hf.no

Soveig Bringsli

CONTACT

solbri@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant

Model Details: Open label, randomized

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: June 7, 2018
• Study Start: April 26, 2018
• Primary Completion: December 1, 2025
• Study Completion: May 1, 2026
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)