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

NCT04552886 | Completed Phase 1 FDA Drug

• 1 other identifier: 8148
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall survival of patients receiving Th-1 dendritic cell immunotherapy

  Minimum 2 years from time of diagnosis

• Progression-free survival of patients receiving Th-1 dendritic cell immunotherapy

  Minimum 2 years from time of diagnosis

Study Arms (4)

Dendritic cell vaccine: Starting dose

EXPERIMENTAL

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

Dendritic cell vaccine dose de-escalation

EXPERIMENTAL

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

Dendritic cell vaccine dose escalation one

EXPERIMENTAL

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

Dendritic cell vaccine dose escalation two

EXPERIMENTAL

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

Interventions

TH-1 Dendritic Cell Immunotherapy BIOLOGICAL

Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.

Dendritic cell vaccine dose de-escalation; Dendritic cell vaccine dose escalation one; Dendritic cell vaccine dose escalation two; Dendritic cell vaccine: Starting dose

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years and older
• 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. \[neoadjuvant therapy is rarely if ever given\]..
• Ability to adhere to the bi-weekly injections of DC vaccine regimen
• 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.
• 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.
• Presented at Tumor Board for review and consensus of Multidisciplinary group to proceed with enrollment.
• Adequate kidney, liver, bone marrow function, and immune function, as follows:
• Hemoglobin ≥ 8.0 gm/dL
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelet count ≥ 100,000 /mm3
• Lymphocyte count greater than 500/L
• 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

You may not qualify if:

• Locally advanced tumors deemed unresectable and/or recurrent tumors after prior vaccination.
• 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.
• 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.
• Patients unwilling or unable to comply with the protocol or provide informed consent.
• 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.
• Concurrent or expected need for therapy with corticosteroids during the vaccination phase of the study.
• Treatment with another investigational drug or other intervention outside of the prespecified standard of care for GBM.
• Patients suffering from active HIV disease.

Sponsors & Collaborators

• The Cooper Health System: lead
• Baylor College of Medicine: collaborator
• Philadelphia College of Osteopathic Medicine: collaborator

Study Sites (2)

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Memorial Hermann- Texas Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Patients, clinicians, investigators and support staff will be aware of the enrollment status of patients in this phase I trial.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will be constructed in a 3+3 algorithm for three steps of dose escalation for a novel GBM-targeting dendritic cell vaccine with rigorous and mandatory safety monitoring.

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 17, 2020
• Study Start: October 11, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: January 11, 2024

Record last verified: 2024-01

Locations

US (2)