Dendritic Cell Cancer Vaccine for High-grade Glioma

NCT01213407 | Completed Phase 2

• 1 other identifier: GBM-Vax-TRX2
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 8

Brief Summary

A randomised, open-label, 2-arm, multi-centre, phase II clinical study with one group receiving standard therapy with Temozolomide, radiotherapy, and Trivax; and a control group receiving standard therapy with Temozolomide and radiotherapy only; after tumour resection of at least 70% in both groups. The hypothesis is based on the assumption that time to progression will be doubled in the treatment group.

Conditions

Glioblastoma Multiforme

Keywords

Dendritic cell; Cancer vaccine; Anti-tumor immune therapy; Interleukine-12; Individualised autologous therapy; Brain cancer; Temozolomide; Radiotherapy; Irradiation; High-grade glioma; Advanced therapy medicinal product ATMP; Somatic cell therapy; Leukocyte apheresis; Neurosurgery; Neurooncology; Neurology; Immunology; Tumor immunology; Transfusion medicine; Monocyte; Killer cell; Cytotoxic T-cell; Cytotoxic T-lymphocyte

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival measured as percentage of non-progressive patients with newly diagnosed GBM 12 months after a post-operative MRI scan treated according to the current standard (surgical resection, irradiation, oral chemotherapy with Temozolomide), and Trivax, an autologous DC cancer vaccine charged with autologous tumour protein, as add-on therapy (group A), in comparison to patients receiving standard treatment without Trivax (group B).

  12 months

Secondary Outcomes (3)

• Quality of Life

  24 months

• Progression free survival at 18 and 24 months

  24 months

• Overall survival

  24 months

Study Arms (2)

Standard therapy plus Trivax

EXPERIMENTAL

Standard therapy with Surgery, Temozolomide, and Radiotherapy; plus Trivax, 5x10e6 autologous interleukine-12 secreting dendritic cells charged with autologous tumour lysate.

Drug: Trivax, Temozolomide, Surgery, Radiotherapy

Standard therapy

ACTIVE COMPARATOR

Surgery, Temozolomide, Radiotherapy

Drug: Temozolomide, Surgery, Radiotherapy

Interventions

Trivax, Temozolomide, Surgery, Radiotherapy DRUG

Trivax: 5 x 10e6 dendritic cells, intranodal in 500 µl NaCl, weeks 7, 8, 9, 10, 12, 16, 20, 24, 28, 32 Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6. Break: weeks 7, 8, 9, 10. Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31.

Standard therapy plus Trivax

Temozolomide, Surgery, Radiotherapy DRUG

Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6 Break: weeks 7, 8, 9, 10 Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31

Standard therapy

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male, paediatric or adult patients of 3 to 70 years of age at time of diagnosis that qualify for standard treatment including surgery, Temozolomide and radiotherapy.
• GBM (WHO IV), confirmed by histology.
• Total, subtotal, or partial resection of more then 70% of tumour mass defined by MRI.
• Supratentorial tumour localisation.
• ECOG performance status 0, 1, or 2 (for study patients older 18 years).
• Life expectancy of at least 12 weeks by assessment of the attending physician.
• Written informed consent of patient and/or legal guardian in case of children or adolescents.

You may not qualify if:

• Less than 100 µg of tumour protein obtained from the resected tissue.
• Anti-neoplastic chemotherapy or radiotherapy during 4 weeks before entering the study, e.g. in another therapeutic phase I, II, or III study.
• Positive pregnancy test or breast-feeding.
• Patients unwilling to perform a save method of birth control.
• Known hypersensitivity to temozolomide.
• HIV positivity.

Sponsors & Collaborators

• Activartis Biotech: lead

Study Sites (8)

Landesnervenklinik Wagner-Jauregg

Linz, Upper Austria, 4020, Austria

Location

Landeskrankenhaus Feldkirch

Feldkirch, 6807, Austria

Location

Department of Neurosurgery, Medical University Graz

Graz, 8036, Austria

Location

Clinical Department of Neurology, Medical University Innsbruck

Innsbruck, 6020, Austria

Location

Department of Neurosurgery, Christian Doppler Klinik, Paracelsus Medizinische Privatuniversität

Salzburg, 5020, Austria

Location

Neuroonkologisches Tumorboard KFJ-KA; Rudolfsstiftung

Vienna, 1030, Austria

Location

Department of Paediatrics, Medical University Vienna

Vienna, 1090, Austria

Location

Medical Department of Oncology, Donauspital, SMZ-Ost

Vienna, 1220, Austria

Location

Related Publications (6)

• Dohnal AM, Graffi S, Witt V, Eichstill C, Wagner D, Ul-Haq S, Wimmer D, Felzmann T. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines. J Cell Mol Med. 2009 Jan;13(1):125-35. doi: 10.1111/j.1582-4934.2008.00304.x. Epub 2008 Mar 17.

  PMID: 18363835 BACKGROUND

• Dohnal AM, Witt V, Hugel H, Holter W, Gadner H, Felzmann T. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy. 2007;9(8):755-70. doi: 10.1080/14653240701589221. Epub 2007 Oct 4.

  PMID: 17917887 BACKGROUND

• Felzmann T, Huttner KG, Breuer SK, Wimmer D, Ressmann G, Wagner D, Paul P, Lehner M, Heitger A, Holter W. Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses. Cancer Immunol Immunother. 2005 Aug;54(8):769-80. doi: 10.1007/s00262-004-0637-2. Epub 2005 Jan 13.

  PMID: 15647926 BACKGROUND

• Huttner KG, Breuer SK, Paul P, Majdic O, Heitger A, Felzmann T. Generation of potent anti-tumor immunity in mice by interleukin-12-secreting dendritic cells. Cancer Immunol Immunother. 2005 Jan;54(1):67-77. doi: 10.1007/s00262-004-0571-3.

  PMID: 15693141 BACKGROUND

• Michael Dohnal A, Luger R, Paul P, Fuchs D, Felzmann T. CD40 ligation restores type 1 polarizing capacity in TLR4-activated dendritic cells that have ceased interleukin-12 expression. J Cell Mol Med. 2009 Aug;13(8B):1741-1750. doi: 10.1111/j.1582-4934.2008.00584.x.

  PMID: 20187300 BACKGROUND

• Traxlmayr MW, Wesch D, Dohnal AM, Funovics P, Fischer MB, Kabelitz D, Felzmann T. Immune suppression by gammadelta T-cells as a potential regulatory mechanism after cancer vaccination with IL-12 secreting dendritic cells. J Immunother. 2010 Jan;33(1):40-52. doi: 10.1097/CJI.0b013e3181b51447.

  PMID: 19952957 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Glioma

Interventions

Temozolomide; Surgical Procedures, Operative; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Johanna Buchroithner, MD

  Landesnervenklinik Wagner-Jauregg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: October 4, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 19, 2016

Record last verified: 2016-05

Locations

AU (8)