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

Primary Purpose

Glioblastoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TH-1 Dendritic Cell Immunotherapy
Sponsored by
The Cooper Health System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cooper University HospitalRecruiting
  • Memorial Hermann- Texas Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dendritic cell vaccine: Starting dose

Dendritic cell vaccine dose de-escalation

Dendritic cell vaccine dose escalation one

Dendritic cell vaccine dose escalation two

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Safety and potential toxicity of Th-1 dendritic cell immunotherapy
Patients will be monitored for adverse events as dictated by CTCAE version 5.

Secondary Outcome Measures

Overall survival of patients receiving Th-1 dendritic cell immunotherapy
Length of survival for patients who receive this vaccine will be tabulated.
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

Full Information

First Posted
September 11, 2020
Last Updated
June 27, 2022
Sponsor
The Cooper Health System
Collaborators
Baylor College of Medicine, Philadelphia College of Osteopathic Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04552886
Brief Title
Dendritic Cell Vaccination With Standard Postoperative Chemoradiation for the Treatment of Adult Glioblastoma
Official Title
A Phase I Study of Th-1 Dendritic Cell Immunotherapy in Combination With Standard Chemoradiation for the Adjuvant Treatment of Adult Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cooper Health System
Collaborators
Baylor College of Medicine, Philadelphia College of Osteopathic Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Masking Description
Patients, clinicians, investigators and support staff will be aware of the enrollment status of patients in this phase I trial.
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dendritic cell vaccine: Starting dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Dendritic cell vaccine dose de-escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Dendritic cell vaccine dose escalation one
Arm Type
Experimental
Arm Description
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.
Arm Title
Dendritic cell vaccine dose escalation two
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
TH-1 Dendritic Cell Immunotherapy
Intervention Description
Adult patients with histopathologically diagnosed glioblastoma will be eligible for this novel, personalized dendritic cell vaccine after completing standard of care chemoradiation.
Primary Outcome Measure Information:
Title
Safety and potential toxicity of Th-1 dendritic cell immunotherapy
Description
Patients will be monitored for adverse events as dictated by CTCAE version 5.
Time Frame
Two years
Secondary Outcome Measure Information:
Title
Overall survival of patients receiving Th-1 dendritic cell immunotherapy
Description
Length of survival for patients who receive this vaccine will be tabulated.
Time Frame
Minimum 2 years from time of diagnosis
Title
Progression-free survival of patients receiving Th-1 dendritic cell immunotherapy
Description
If there is tumor recurrence, the time from diagnosis until recurrence will be collected
Time Frame
Minimum 2 years from time of diagnosis

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alan R Turtz, MD
Phone
856-342-3385
Email
turtz-alan@cooperhealth.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph F Georges, DO, PhD
Phone
602-999-3382
Email
Joseph.Georges@asu.edu
Facility Information:
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alan R Turtz, MD
Phone
856-342-3385
Email
turtz-alan@cooperhealth.edu
First Name & Middle Initial & Last Name & Degree
Joseph F Georges, DO, PhD
Phone
602-999-3382
Email
Joseph.Georges@asu.edu
Facility Name
Memorial Hermann- Texas Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoshua Esquenazi, MD
Phone
713-486-8088
Email
Yoshua.EsquenaziLevy@uth.tmc.edu
First Name & Middle Initial & Last Name & Degree
Sigmund Hsu, MD
Phone
713-486-8051
Email
Sigmund.Hsu@uth.tmc.edu

12. IPD Sharing Statement

Learn more about this trial

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

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