Dendritic Cell Vaccination With Standard Postoperative Chemoradiation for the Treatment of Adult Glioblastoma

A Phase I Study of Th-1 Dendritic Cell Immunotherapy in Combination With Standard Chemoradiation for the Adjuvant Treatment of Adult Glioblastoma

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: TH-1 Dendritic Cell Immunotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alan R Turtz, MD; Phone Number: 856-342-3385; Email: turtz-alan@cooperhealth.edu
• Study Contact Backup: Name: Joseph F Georges, DO, PhD; Phone Number: 602-999-3382; Email: Joseph.Georges@asu.edu

Study Locations

• United States
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann- Texas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 glioblastoma (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. Eastern Cooperative Oncology Group (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 temozolomide (TMZ). The use of a tumor treatment field (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dendritic cell vaccine: Starting dose; This 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.	Biological: TH-1 Dendritic Cell Immunotherapy; Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.
Experimental: Dendritic cell vaccine dose de-escalation; If 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.	Biological: TH-1 Dendritic Cell Immunotherapy; Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.
Experimental: Dendritic cell vaccine dose escalation one; If 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.	Biological: TH-1 Dendritic Cell Immunotherapy; Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.
Experimental: Dendritic cell vaccine dose escalation two; If 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.	Biological: TH-1 Dendritic Cell Immunotherapy; Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Cooper Health System
• Collaborators: Baylor College of Medicine; Philadelphia College of Osteopathic Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: 8148 (CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No