Efficiency of Vaccination with Lysate-loaded Dendritic Cells in Patients with Newly Diagnosed Glioblastoma

NCT ID: NCT03395587

Last Updated: 2024-12-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-06
• Study Completion Date: 2027-05-31

Brief Summary

The primary objective of the study is to determine whether overall survival of newly diagnosed glioblastoma patients treated with lysate-loaded, mature dendritic cell vaccines as add-on to the standard of care consisting of resection, radiotherapy with concomitant temozolomide chemotherapy and subsequent adjuvant temozolomide chemotherapy is superior to the treatment with the standard of care alone.

Detailed Description

This is a multicenter, randomized, phase 2 study, integrating vaccination with tumorlysate-loaded mature dendritic cells into standard radio/temozolomide-chemotherapy of newly diagnosed glioblastoma patients with near-complete resection after fluorescence-guided resection. Only patients with confirmed gross-total resection and a residual tumor volume below 5 ml will be eligible for the trial. Vaccination will be performed after radio- and concomitant temozolomide chemotherapy and during the first three cycles of adjuvant TMZ.

Conditions

Glioblastoma

Study Design

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

Study Groups

Experimental intervention

Fluorescence-guided surgery (day 0) Leukapheresis (wk4) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) vaccination with autologous, tumor lysate-loaded, mature dendritic cells (DC) (7x, 2 - 10 x 106 DC each, intradermal injection, weekly wk11-14, wk17, 21, 25)Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)

Group Type: EXPERIMENTAL

Autologous, tumor lysate-loaded, mature dendritic cells (DC)

Intervention Type: BIOLOGICAL

Advanced therapy medicinal product (ATMP) produced at the University Hospital Düsseldorf according to Good Manufacturing Practice (GMP) with production permission according §13 AMG (German Drug Law) of the local authorities (Bezirks¬regierung Düsseldorf)

Control intervention

Standard therapy:

Fluorescence-guided surgery (day 0) Fractionated radiotherapy (60 Gy: 2 Gy/d, 5/7 d, 6 wks; wk5 10) and concomitant TMZ chemotherapy (75 mg/m2/d; 6 wks; wk5-10) Adjuvant TMZ chemotherapy (150-200 mg/m2/d, 6x, days 1 5 of 28 d cycle: wk15, 19, 23, 27, 31, 35)

Group Type: OTHER

standard therapy

Intervention Type: DRUG

temozolomide, fractionated radiochemotherapy

Interventions

Autologous, tumor lysate-loaded, mature dendritic cells (DC)

Advanced therapy medicinal product (ATMP) produced at the University Hospital Düsseldorf according to Good Manufacturing Practice (GMP) with production permission according §13 AMG (German Drug Law) of the local authorities (Bezirks¬regierung Düsseldorf)

Intervention Type: BIOLOGICAL

standard therapy

temozolomide, fractionated radiochemotherapy

Intervention Type: DRUG

Other Intervention Names

dendritic cell vaccination; temozolomide, fractionated radiochemotherapy

Eligibility Criteria

Inclusion Criteria

Determined at pre-screening (prior to surgery; wk-3 - wk-1):

• Patients ≥ 18 years of age at surgery.
• Patients must be in a cognitive state to understand and sign the informed consent indicating that they are aware of the investigational nature and procedures of the study.
• First written informed consent for screening for eligibility, including tumor tissue collection, transfer and processing, central neuropathological evaluation of Tumor sample, central neuroradiological assessment of extent of resection, infectious disease (HIV, HBV, HCV, Treponema pallidum) testing, determination of MGMT promoter methylation status and pregnancy testing.

Determined at screening (at and post-surgery; d0 - wk3):

• Newly diagnosed, monofocal GBM, IDH wildtype (WHO grade IV), including the histological variants of gliosarcoma and giant cell glioblastoma, confirmed by central neuropathologist according to the WHO classification of central nervous System tumors 2016. Tumors may cross into, but not beyond the corpus callosum.
• Near-complete resection (≤ 5 ml residual contrast enhancing tumor volume) confirmed by central neuroradiologist on MRI scan within 72 h postoperative; awake surgery and second look surgery are possible, if medically indicated.
• Sterile tumor sample of ≥ 150 mg with tumor cell frequency ≥ 60% as determined by central neuropathologist available for vaccine production.
• Successful production of sterile, avital tumor lysate.
• Karnofsky performance status ≥ 70%.
• Adequate hepatic (serum glutamate pyruvate transferase/alanine transaminase (SGPT/ALT), serum glutamic oxaloacetate transaminase/aspartate transaminase (SGOT/AST) and alkaline phosphatase ≤ 3-times upper limit of normal (ULN); bilirubin ≤ 1.5-times ULN) and renal functions (creatinine ≤ 1.5-times ULN).
• Adequate bone marrow function (hemoglobin ≥ 10 g/dl, thrombocytes ≥ 100,000/μl, white blood cell count ≥ 3,000/μl; neutrophil count ≥ 1,500/μl).
• Prothrombin time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x ULN unless therapeutically warranted. International normalized ratio (INR) (in absence of anticoagulation treatment) ≤ 1.5.
• Systemic corticosteroids tapered down to ≤ 2 mg of dexamethasone or equivalent per day within 7 days postoperative (use of corticosteroids during the treatment period should be avoided, however it is possible if clinically indicated, but may require interruption of dendritic cell vaccination).
• Female patients with reproductive potential and male generative patients and their female partners must agree to be true abstinent or to use a highly effective form of contraception (pearl index < 1%) during the trial.
• Patients must be in a cognitive state to understand and sign the informed consent indicating that they are aware of the investigational nature and procedures of the study.
• Written informed consent to participate in study.

Exclusion Criteria

determined at pre-screening (prior to surgery; wk-3 - wk-1):

• Medical history of severe acute or chronic disease with poor prognosis, e.g. severe coronary heart disease, heart failure (New York Heart Association classes III/IV), severe poorly controlled diabetes, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
• Medical history of severe autoimmune disorder or immunodeficiency or patients with organ allograft.
• Medical history of bleeding diathesis or coagulopathy.
• Prior malignancy during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with prostate-specific antigen (PSA) level less than ULN.
• Previous radiotherapy to head and neck.
• Known allergy or intolerability to TMZ, dacarbazine, the contrast agent or to components of the dendritic cell vaccine.
• Current treatment of glioblastoma in another clinical trial with therapeutic intervention or current use of any other investigational agent.
• Known pregnancy or breast feeding.
• No known severe infection requiring treatment.
• Accommodation in an institution due to legal orders (§40(4) AMG).
• Evidence of current drug or alcohol abuse. determined at screening (at and post-surgery; d0 - wk3):
• Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum or other severe infection requiring treatment.
• Accommodation in an institution due to legal orders (§40(4) AMG).
• Pregnant or breast feeding female patients. From pre-menopausal female patients with childbearing potential a negative pregnancy test must be obtained.
• Any psycho-social condition hampering compliance with the study protocol.
• MGMT promoter methylation status equivocal.

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

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Sabel, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery

Locations

Klinik für Neurologie, Knappschaftskrankenhaus Bochum

Bochum, North Rhine-Westphalia, Germany

Klinik für Neurochirurgie, Sana Kliniken Duisburg

Duisburg, North Rhine-Westphalia, Germany

Neurochirurgische Klinik, Universitätsklinikum Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

St. Marien Hospital Lünen, Klinik für Neurochirurgie

Lünen, North Rhine-Westphalia, Germany

Klinik für Allgemeine Neurologie, Universitätsklinikum Münster

Münster, North Rhine-Westphalia, Germany

Helios Klinikum Krefeld, Klinik für Neurochirurgie

Krefeld, , Germany

Countries

Germany

References

Naulaerts S, Datsi A, Borras DM, Antoranz Martinez A, Messiaen J, Vanmeerbeek I, Sprooten J, Laureano RS, Govaerts J, Panovska D, Derweduwe M, Sabel MC, Rapp M, Ni W, Mackay S, Van Herck Y, Gelens L, Venken T, More S, Bechter O, Bergers G, Liston A, De Vleeschouwer S, Van Den Eynde BJ, Lambrechts D, Verfaillie M, Bosisio F, Tejpar S, Borst J, Sorg RV, De Smet F, Garg AD. Multiomics and spatial mapping characterizes human CD8+ T cell states in cancer. Sci Transl Med. 2023 Apr 12;15(691):eadd1016. doi: 10.1126/scitranslmed.add1016. Epub 2023 Apr 12.

Reference Type: DERIVED

PMID: 37043555 (View on PubMed)

Rapp M, Grauer OM, Kamp M, Sevens N, Zotz N, Sabel M, Sorg RV. A randomized controlled phase II trial of vaccination with lysate-loaded, mature dendritic cells integrated into standard radiochemotherapy of newly diagnosed glioblastoma (GlioVax): study protocol for a randomized controlled trial. Trials. 2018 May 25;19(1):293. doi: 10.1186/s13063-018-2659-7.

Reference Type: DERIVED

PMID: 29801515 (View on PubMed)

Other Identifiers

GlioVax

Identifier Type: -

Identifier Source: org_study_id