Clinical Trials /

Dendritic Cell Vaccination With Standard Postoperative Chemoradiation for the Treatment of Adult Glioblastoma: Phase I Clinical Trial

NCT04552886

Description:

Effective treatments are desperately needed for glioblastoma (GBM) patients. This phase I clinical trial assesses the safety of a novel personalized dendritic-cell vaccine administered to GBM patients shortly after completing standard-of-care treatments. Secondary outcomes will evaluate patient progression-free survival and overall survival.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dendritic Cell Vaccination With Standard Postoperative Chemoradiation for the Treatment of Adult Glioblastoma: Phase I Clinical Trial
  • Official Title: A Phase I Study of Th-1 Dendritic Cell Immunotherapy in Combination With Standard Chemoradiation for the Adjuvant Treatment of Adult Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 8148
  • NCT ID: NCT04552886

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
TH-1 Dendritic Cell ImmunotherapyDendritic cell vaccine dose de-escalation

Purpose

Effective treatments are desperately needed for glioblastoma (GBM) patients. This phase I clinical trial assesses the safety of a novel personalized dendritic-cell vaccine administered to GBM patients shortly after completing standard-of-care treatments. Secondary outcomes will evaluate patient progression-free survival and overall survival.

Detailed Description

      This is a single arm (non-randomized) first-in-man pilot study to evaluate the safety and
      feasibility of delivering a dendritic cell vaccine in nine to twenty-four (n=9-24) adult
      patients diagnosed with glioblastoma (GBM) after undergoing neurosurgical tumor resection,
      and in whom a neuropathological diagnosis has been established. Standard of care chemotherapy
      and radiation therapy shall be followed as per routine neuro-oncologic paradigms after which
      patients enrolled into this study will receive a personalized vaccine beyond standard of
      care. Effective adjuvant therapies are urgently needed for these patients given that standard
      of care is rarely successful in preventing recurrence among GBM patients, nor death among
      relapsed patients with this very poor-prognosis tumor type. The study is constructed in a 3+3
      algorithm for three steps of dose escalation with rigorous and mandatory safety monitoring.
    

Trial Arms

NameTypeDescriptionInterventions
Dendritic cell vaccine: Starting doseExperimentalThis arm will evaluate the safety of administering a total dendritic cell dose of 3.5 x 10^6. A total of 3-6 patients will be enrolled with this dose. If this dose is associated with unacceptable side effects, as detailed in the study protocol, no further patients will be enrolled at this dose.
  • TH-1 Dendritic Cell Immunotherapy
Dendritic cell vaccine dose de-escalationExperimentalIf unacceptable side effects, as detailed in the study protocol, are identified at a total dose of 3.5 x 10^6, then a cohort of 3-6 enrolled patients will receive a de-escalated total dendritic cell dose of 1.75 X 10^6.
  • TH-1 Dendritic Cell Immunotherapy
Dendritic cell vaccine dose escalation oneExperimentalIf no unacceptable side effects, as detailed in the study protocol, are identified at a total dose of 3.5 x 10^6, then a cohort of 3-6 enrolled patients will receive an escalated total dendritic cell dose of 7.0 X 10^6.
  • TH-1 Dendritic Cell Immunotherapy
Dendritic cell vaccine dose escalation twoExperimentalIf no unacceptable side effects, as detailed in the study protocol, are identified at a total dose of 7.0 x 10^6, then a cohort of 3-6 enrolled patients will receive an escalated total dendritic cell dose of 1.4 X 10^7.
  • TH-1 Dendritic Cell Immunotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of signed and dated informed consent form

          2. Stated willingness to comply with all study procedures and availability for the
             duration of the study

          3. Male or female, aged 18 years and older

          4. Diagnosed with GBM deemed to be potentially resectable and who are deemed to be good
             candidate for postoperative adjuvant chemo and radiation therapy. This may include
             patients whose tumors are deemed suitable for gross total resection as well as
             patients whose tumors are deemed partially resectable and who undergo partial
             resection followed by adjuvant therapy. [neoadjuvant therapy is rarely if ever
             given]..

          5. Ability to adhere to the bi-weekly injections of DC vaccine regimen

          6. For females of reproductive potential: use of highly effective contraception for at
             least 1 month prior to screening and agreement to use such a method during study
             participation and for an additional 12 weeks following discontinuations of last
             vaccination. Must have a negative serum pregnancy test prior to first treatment.

          7. For males of reproductive potential: use of condoms or other methods to ensure
             effective contraception with partner during study participation and for an additional
             12 weeks following discontinuations of last vaccination.

          8. Presented at Tumor Board for review and consensus of Multidisciplinary group to
             proceed with enrollment.

          9. Adequate kidney, liver, bone marrow function, and immune function, as follows:

               1. Hemoglobin ≥ 8.0 gm/dL

               2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

               3. Platelet count ≥ 100,000 /mm3

               4. Lymphocyte count greater than 500/L

               5. Glomerular filtration rate (GFR) > 60 mL/min/m2 and Creatinine < 1.5mg/dl

             i. For males = (140 - age[years]) x (body weight [kg]) (72) x (serum creatinine
             [mg/dL] ii. For females = 0.85 x male value f. Total bilirubin ≤ 1.5 times upper limit
             of normal (ULN), g. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT
             (SGPT) ≤ 2.5 times the ULN h. Albumin >2g/dL i. (IgM), surface antibody and antigen,
             Hepatitis B and C antibody. j. Negative HIV status

         10. ECOG performance status ≤ 2.

        Exclusion Criteria:

          1. Locally advanced tumors deemed unresectable and/or recurrent tumors after prior
             vaccination.

          2. Use of non-standard post-operative treatment regimen, as defined by the Stupp
             protocol: postoperative chemoradiation and initiation of TMZ. The use of a TTF device
             with adjuvant TMZ is at the discretion of the investigator.

          3. Female patients who are pregnant, breast feeding, or of childbearing potential without
             a negative pregnancy test prior to baseline. Post-menopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential.

          4. Patients unwilling or unable to comply with the protocol or provide informed consent.

          5. Any severe or uncontrolled medical condition or other condition that could affect
             participation in this study, including but not limited to: hyper/hypothyroidism,
             systemic autoimmune disorders, untreated viral hepatitis or autoimmune hepatitis.

          6. Concurrent or expected need for therapy with corticosteroids during the vaccination
             phase of the study.

          7. Treatment with another investigational drug or other intervention outside of the
             prespecified standard of care for GBM.

          8. Patients suffering from active HIV disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and potential toxicity of Th-1 dendritic cell immunotherapy
Time Frame:Two years
Safety Issue:
Description:Patients will be monitored for adverse events as dictated by CTCAE version 5.

Secondary Outcome Measures

Measure:Overall survival of patients receiving Th-1 dendritic cell immunotherapy
Time Frame:Minimum 2 years from time of diagnosis
Safety Issue:
Description:Length of survival for patients who receive this vaccine will be tabulated.
Measure:Progression-free survival of patients receiving Th-1 dendritic cell immunotherapy
Time Frame:Minimum 2 years from time of diagnosis
Safety Issue:
Description:If there is tumor recurrence, the time from diagnosis until recurrence will be collected

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:The Cooper Health System

Last Updated

September 11, 2020