Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients

NCT02649582 | Active Not Recruiting Phase 1

• 1 other identifier: CCRG14-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase I/II trial, the primary objective is to determine overall and progression-free survival of patients with newly diagnosed glioblastoma when autologous Wilms' tumor 1 (WT1) messenger (m)RNA-loaded dendritic cell (DC) vaccination is added to adjuvant temozolomide maintenance treatment following (sub)total resection and temozolomide-based chemoradiation.

Conditions

Glioblastoma Multiforme of Brain

Keywords

Dendritic cells; Chemoimmunotherapy; Adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Patients will be followed for survival, from apheresis (\~ diagnosis), for which the accurate date and reason of death (cancer-related or non-related) will be recorded for every patient.

  Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later

Secondary Outcomes (5)

• Number of glioblastoma patients post surgical resection with feasible and safe DC vaccine production

  Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)

• Feasibility of DC vaccine administration to glioblastoma patients combined with chemotherapy

  Upon maintenance chemotherapy treatment (i.e. +/- 12 weeks post leukapheresis)

• Number of participants with adverse events as a measure of safety and tolerability

  Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later

• Immunological responses to the DC vaccine

  At first DC vaccination + day 1 of first and fourth temozolomide treatment cycles

• Objective clinical responses by tumor evaluation (clinical efficacy)

  Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later

Other Outcomes (1)

• General and disease-specific quality of life

  Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later

Study Arms (1)

Single Arm

EXPERIMENTAL

Dendritic cell vaccine plus temozolomide chemotherapy

Biological: Dendritic cell vaccine plus temozolomide chemotherapy

Interventions

Dendritic cell vaccine plus temozolomide chemotherapy BIOLOGICAL

When eligible after total or subtotal resection (as assessed by neurosurgeon and post-operative brain MRI): 1. Leukocyte apheresis (before chemoradiation): for DC vaccine production 2. Chemoradiation (standard treatment: initiated as soon as the patient's hematological blood values are adequate after apheresis): 2 Gy once daily 5 days/week for 6 weeks with 75 mg/m² temozolomide daily from the first until the last day of radiotherapy (no longer than 49 days in total) 3. Induction immunotherapy: intradermal vaccination with autologous WT1 mRNA-loaded DCs weekly (+/-1 day) for 3 weeks, starting ≥ 1 week after radiotherapy 4. Chemo-immunotherapy: 150-200 mg/m²/d temozolomide days 1-5 every 28 days +/- 2 days (max. 12 months) starting ≥3 days after the third vaccine of the induction immunotherapy + DC vaccination on day 21±3 days of every 28-day cycle

Single Arm

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, histologically verified glioblastoma (WHO grade IV)
• Aged ≥ 18 years
• Total or subtotal resection:
• Total resection: macroscopic complete resection as assessed by the neurosurgeon and absence of any residual contrast-enhancing mass on post-operative (≤ 72h) brain MRI
• Subtotal resection: macroscopic complete resection as assessed by the neurosurgeon, but with residual contrast-enhancement ≤ 2 cm³ on post-operative (≤ 72h) brain MRI
• Signed informed consent
• Willing and able to comply with the protocol as judged by the Investigator
• Estimated to start with chemoradiation ≥ 28 days and ≤ 49 days following surgical resection
• Fit to undergo: leukapheresis, chemoradiation, chemotherapy and immunotherapy
• No corticosteroid treatment ≤ 1 week before apheresis
• WHO performance status ≤ 2
• Life expectancy ≥ 3 months as estimated by the Investigator

You may not qualify if:

• History of another malignancy, except for adequately controlled basal cell skin carcinoma, squamous skin carcinoma, or carcinoma in situ of the uterine cervix or unless the investigator rationalizes otherwise
• Prior radiation or chemotherapy
• Any pre-existing contraindication for temozolomide treatment
• Any pre-existing contraindication for contrast-enhanced brain MRI
• Pregnant or breast-feeding
• Documented immune deficiency or systemic immune-suppressive treatment
• Known positive viral serology for HIV, HBV, HCV, or syphilis
• Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of the vaccine, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Location

Related Publications (10)

• Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.

  PMID: 20631300 BACKGROUND

• Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.

  PMID: 19530029 BACKGROUND

• Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.

  PMID: 22291091 BACKGROUND

• Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.

  PMID: 19656053 BACKGROUND

• Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014 Jun;15(7):e257-67. doi: 10.1016/S1470-2045(13)70585-0.

  PMID: 24872109 BACKGROUND

• Anguille S, Smits EL, Bryant C, Van Acker HH, Goossens H, Lion E, Fromm PD, Hart DN, Van Tendeloo VF, Berneman ZN. Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy. Pharmacol Rev. 2015 Oct;67(4):731-53. doi: 10.1124/pr.114.009456.

  PMID: 26240218 BACKGROUND

• Willemen Y, Huizing MT, Smits E, Anguille S, Nijs G, Stein B, Van Tendeloo V, Peeters M, Berneman Z. J Clin Oncol 30(suppl): abstr e13051, 2012.

  BACKGROUND

• Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22.

  PMID: 28830889 BACKGROUND

• Z. Berneman, A. Van de Velde, S. Anguille, Y. Willemen, M. Huizing, P. Germonpré, K. Saevels, G. Nijs, N. Cools, A. Van Driessche, B. Stein, H. De Reu, W. Schroyens, A. Gadisseur, A. Verlinden, K. Vermeulen, M. Maes, M. Lammens, H. Goossens, M. Peeters, V. Van Tendeloo, E. Smits. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma. Cytotherapy 2016, 18(6), p. S13-14

  BACKGROUND

• Z. Berneman, S. Anguille, Y. Willemen, A. Van de Velde, P. Germonpré, M. Huizing, V. Van Tendeloo, K. Saevels, L. Rutsaert, K. Vermeulen, A. Snoeckx, B. Op de Beeck, N. Cools, G. Nijs, B. Stein, E. Lion, A. van Driessche, M. Peeters, E. Smits. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the Wilms' Tumor protein (WT1): correlation of clinical effect and overall survival with T-cell response. Cytotherapy 2019, 21(5), p. S10.

  BACKGROUND

Study Officials

• Zwi N Berneman, MD, PhD

  Antwerp University Hospital, Division of Hematology and Center for Cell Therapy and Regenerative Medicine

  STUDY DIRECTOR

• Marika Rasschaert, MD, PhD

  Antwerp University Hospital (UZA), Division of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 7, 2016
• Study Start: December 1, 2015
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 4, 2026

Record last verified: 2026-06

Locations

BE (1)