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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT03395587

Studienbeginn:
März 2018

Letztes Update:
23.12.2022

Wirkstoff:
Autologous, tumor lysate-loaded, mature dendritic cells (DC), standard therapy

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Heinrich-Heine University, Duesseldorf

Collaborator:
German Federal Ministry of Education and Research

Studienleiter

Michael Sabel, Prof. MD
Principal Investigator
Department of Neurosurgery

Kontakt

Michael Sabel, Prof. MD
Kontakt:
Phone: +49 211 8116276
E-Mail: Michael.Sabel@med.uni-duesseldorf.de» Kontaktdaten anzeigen

Marion Rapp, PD MD
Kontakt:
Phone: +49 211 8107458
E-Mail: Marion.Rapp@med.uni-duesseldorf.de» Kontaktdaten anzeigen

Studienlocations
(3 von 6)

Klinik für Neurologie, Knappschaftskrankenhaus Bochum
44829 Bochum
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Uwe Schlegel, Prof. MD
Phone: 00492342993719
E-Mail: neurologie@kk-bochum.de

Rekowski Sylvia
Phone: 00492342993719
E-Mail: sylvia.rekowski@kk-bochum.de» Ansprechpartner anzeigen

Klinik für Neurochirurgie, Sana Kliniken Duisburg
47055 Duisburg
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Jung Su Zin, Dr. med.
Phone: 00492037332401
E-Mail: suzin.jung@sana.de» Ansprechpartner anzeigen

Neurochirurgische Klinik, Universitätsklinikum Düsseldorf
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael C. Sabel, Prof. MD
Phone: 00492118116276
E-Mail: michael.sabel@med.uni-duesseldorf.de

Natalie Sevens
Phone: 00492118117881» Ansprechpartner anzeigen

Klinik für Allgemeine Neurologie, Universitätsklinikum Münster
48149 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Oliver Grauer, PD Dr. med.
Phone: 0492518346814
E-Mail: oliver.grauer@ukmuenster.de» Ansprechpartner anzeigen

St. Marien Hospital Lünen, Klinik für Neurochirurgie
44534 Lünen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Konstantinos Gousias, PD Dr. Dr.
Phone: +49230677
Phone (ext.): 3151
E-Mail: cn@klinikum-luenen.de» Ansprechpartner anzeigen

Helios Klinikum Krefeld, Klinik für Neurochirurgie
47805 Krefeld
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael Stoffel, Prof. MD
Phone: +492151321320
E-Mail: Michael.Stoffel@helios-gesundheit.de» Ansprechpartner anzeigen

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Overall survival (OS) (Time Frame - Day of surgery until death of any cause assessed up to 34 months):
Overall survival as measured from the day of surgery until death from any cause assessed up to 34 months

Secondary outcome:

1. Progression free survival (PFS) (Time Frame - Day of surgery until day of diagnosis of tumor progression assessed upto 34 months):
Progression-free survival as measured from the day of surgery until diagnosis of tumor progression by MRI scan according to modified Response Assessment in Neuro-Oncology (RANO) criteria assessed up to 34 months

2. OS rates (Time Frame - 6, 12 and 24 months after the day of surgery):
OS rates at 6, 12 and 24 months after the day of surgery

3. PFS rates (Time Frame - 6, 12 and 24 months after the day of surgery):
PFS rates at 6, 12 and 24 months after the day of surgery

4. Frequency and severity of adverse events (Time Frame - 34 months):
Safety based on the frequency and severity of adverse events (AE) with toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 4.03 (CTCAE 4.03)

5. Karnofsky Performance Status (Time Frame - 34 months):
Overall and neurological performance based on the Karnofsky performance status (MMSE-2)

6. MMSE-2 (Time Frame - 34 months):
Overall and neurological performance based on the Minimal Mental State Examination 2 (MMSE-2)

7. Quality of life of cancer patients (Time Frame - 34 months):
Quality of life as determined by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 3.0

8. Quality of life in patients with brain cancer (Time Frame - 34 months):
Quality of life as determined by the European Organization for Research and Treatment of Cancer (EORTC) Brain Cancer Module QLQ-BN20

9. Psychological distress in oncology patients (Time Frame - 34 months):
Quality of life as determined by the Distress Thermometer (DT)

10. Psychological distress, anxiety and depression (Time Frame - 34months):
Quality of life as determined by the Hospital Anxiety and Depression Scale (HADS) for psycho-oncological strain assessment

Studien-Arme

Experimental: 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)
Other: 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)

Geprüfte Regime

Autologous, tumor lysate-loaded, mature dendritic cells (DC) (dendritic cell vaccination):
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)
standard therapy (temozolomide, fractionated radiochemotherapy):
temozolomide, fractionated radiochemotherapy

Quelle: ClinicalTrials.gov

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