Clinical Trials /

Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients

NCT02649582

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Dendritic Cell-immunotherapy Plus Temozolomide in Glioblastoma Patients
  • Official Title: Adjuvant Dendritic-Cell Immunotherapy Plus Temozolomide Following Surgery and Chemoradiation in Patients With Newly Diagnosed Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CCRG14-001
  • NCT ID: NCT02649582

Conditions

  • Glioblastoma Multiforme of Brain

Interventions

DrugSynonymsArms
Dendritic cell vaccine plus temozolomide chemotherapySingle Arm

Purpose

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) and the Division of Hematology, both headed by Prof. Zwi
      Berneman.

      Recruitment began in December 2015 and is intended to continue until the end of 2020 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.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalDendritic cell vaccine plus temozolomide chemotherapy
  • Dendritic cell vaccine plus temozolomide chemotherapy

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of glioblastoma patients post surgical resection with feasible and safe DC vaccine production
Time Frame:Vaccine production and quality testing (i.e. 4 weeks after leukapheresis)
Safety Issue:
Description:Production of autologous DC vaccines from newly diagnosed glioblastoma patients that underwent maximal, safe surgical resection will be evaluated for: feasibility, assessed by success of leukapheresis and production of sufficient and qualified (phenotypic and functional requirements) vaccines. Safety, assessed by microbiological testing (bacteria, yeast, fungi, mycoplasma, endotoxin) of the DC vaccines.
Measure:Feasibility of DC vaccine administration to glioblastoma patients combined with chemotherapy
Time Frame:Upon maintenance chemotherapy treatment (i.e. +/- 12 weeks post leukapheresis)
Safety Issue:
Description:Administration of 3 weekly DC vaccines following adjuvant chemoradiation (induction phase) and additional DC vaccination at day 21 of each maintenance chemotherapy cycle (booster phase) will be evaluated for feasibility, assessed by successful DC vaccine administration of the proposed treatment scheme.
Measure:Number of participants with adverse events as a measure of safety and tolerability
Time Frame:Through study completion with follow-up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Safety Issue:
Description:Monitoring the incidence of adverse events to evaluate the safety profile and tolerability of the treatment. The severity of adverse events will be assessed according to the NCI CTCAE scale (v4.03, published June 14, 2010).
Measure:Immunological responses to the DC vaccine
Time Frame:At first DC vaccination + day 1 of first and fourth temozolomide treatment cycles
Safety Issue:
Description:Immunological responses to the vaccine will be evaluated ex vivo. Blood samples will be collected from patients on the day of the first DC vaccine, and on day 1 of the first and fourth maintenance temozolomide treatment cycles and will be examined for cell subset distribution and activation status and antigen-specific immunity.
Measure:Objective clinical responses by tumor evaluation (clinical efficacy)
Time Frame:Through study completion with follow up until 90 days after final DC vaccine administration or 24 months after apheresis, whichever occurs later
Safety Issue:
Description:Disease evolution and progression-free survival will be assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria, based on imaging findings (MRI, CT), clinical status and corticosteroid use. Disease will be assessed following chemoradiation (≤ 2 weeks after completing chemoradiation), after every two cycles of temozolomide maintenance treatment and at least every 12 weeks during the booster phase, and every 9-12 weeks during follow-up after treatment discontinuation.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital, Antwerp

Trial Keywords

  • Dendritic cells
  • Chemoimmunotherapy
  • Adjuvant therapy

Last Updated

December 6, 2019