Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients

NCT ID: NCT02649582

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2025-12-31

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.

Detailed Description

Glioblastoma multiforme (GBM), a microscopically infiltrative disease, is the most common malignant brain tumor worldwide. Despite optimized standard of care treatment median survival and prognosis remain poor with a median survival of only 15% and five year survival after diagnosis of 5%.

In this single arm single centre phase I/II trial the investigators will determine the overall and progression free survival of patients with newly diagnosed GBM when autologous WT1 mRNA loaded dendritic cell vaccination is added to standard of care treatment. During recruitment, the investigators will include 20 patients with newly diagnosed, histologically verified glioblastoma (WHO grade IV) who have received a total or subtotal resection of the tumor. Patients who underwent prior radiation or chemotherapy or with a history of other malignancy will be excluded. In addition to standard of care consisting of adjuvant chemoradiation with temozolomide and temozolomide maintenance patients will receive an intradermal vaccination with autologous WT1 mRNA-loaded dendritic cells commencing 1 week after radiotherapy. The dendritic cell therapy product will be generated and administered in the Antwerp University Hospital, more specifically the Center for Cell Therapy and Regenerative Medicine (CCRG), headed by Prof. Zwi Berneman and the Division of Hematology.

Recruitment began in December 2015 and is intended to continue until the end of 2024 or when 20 patients are enrolled. After a follow-up period (until 90 days after final DC vaccine administration or 24 months after apheresis , whichever occurs later), overall and progression free survival analysis will be performed and this will be compared with the published data of standard of care treatment without vaccination. In addition the investigators will look for feasibility, incidence of adverse events and immunogenicity.

Conditions

Glioblastoma Multiforme of Brain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Dendritic cell vaccine plus temozolomide chemotherapy

Group Type: EXPERIMENTAL

Dendritic cell vaccine plus temozolomide chemotherapy

Intervention Type: 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

Interventions

Dendritic cell vaccine plus temozolomide chemotherapy

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Zwi Berneman

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zwi N Berneman, MD, PhD

Role: STUDY_DIRECTOR

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

Marika Rasschaert, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Antwerp University Hospital (UZA), Division of Oncology

Locations

Antwerp University Hospital

Edegem, Antwerp, Belgium

Countries

Belgium

References

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Reference Type: BACKGROUND

PMID: 20631300 (View on PubMed)

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.

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Reference Type: 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.

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Other Identifiers

CCRG14-001

Identifier Type: -

Identifier Source: org_study_id