Back to resultsVaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
Primary Purpose
Brain Tumor, Glioblastoma, Medulloblastoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dendritic Cells
Imiquimod
Sponsored by
About this trial
This is an interventional treatment trial for Brain Tumor focused on measuring Brain tumor, Immunotherapy, Glioma
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed brain tumors (glioblastoma multiforme, anaplastic astrocytoma, medullo
- Age 0 through 17 years (pediatric subjects), and 18 years and above (adult subjects)
- Lansky score of ≥ 60 (0-15 years) or Karnofsky (16 years or older) performance score of ≥ 60%
Adequate organ function within 14 days of study registration including the following:
- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0 x 10^9/L, platelets ≥100 x 10^9/L; hemoglobin ≥ 8 g/dL
- Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
- Renal: Normal serum creatinine for age (below) or creatinine clearance >60 ml/min/1.73 m^2.
- Sexually active women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active men must agree to use barrier contraceptive for the duration of the vaccination period.
- Willingness to travel to participate in study if from outside local region.
- Voluntary written informed consent must be obtained from all patients (if of assent age) and their parents or legal guardians before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Exclusion criteria:
- Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Currently receiving any other investigational agents.
- History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression).
- Any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
Sites / Locations
- Masonic Cancer Center, University of Minnesota
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose Level 3
Dose Level 2
Dose Level 1
Arm Description
15 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
10 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
5 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose
To determine the safety and maximum tolerated dose (MTD) of dendritic cells (DCs) loaded with brain tumor stem cells (BTSCs) as a source of tumor antigen for immunotherapy in children and adults with recurrent GBM, ependymoma or medulloblastoma brain tumors. Toxicity is determined using the criteria established by the National Cancer Institute's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE).
Secondary Outcome Measures
Time to Tumor Progression
To determine time to tumor progression in this patient population - exhibit a prolonged time to tumor progression by the absence of tumor growth as determined by MRI.
Full Information
NCT ID
NCT01171469
First Posted
July 27, 2010
Last Updated
November 29, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT01171469
Brief Title
Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
Official Title
Phase I Study of Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Recurrent or Progressive Malignant Gliomas
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single center Phase I study to determine the safety and maximum tolerated dose (MTD) of autologous dendritic cells (DCs) loaded with allogeneic brain tumor stem cells administered as a vaccination in children and adults with recurrent brain tumors. Once the MTD has been determined, we will conduct a phase II study to determine efficacy.
Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately, at the present time the majority of tumor patients are unable to mount an adequate immune response and thus succumb to their tumors. We postulate that the inability to generate an appropriate immune response in these patients is due to a lack of sufficient numbers of appropriate T cells due to an inadequate source of tumor antigens.
Detailed Description
Autologous DCs will be obtained from peripheral blood mononuclear cells (PBMCs) from each patient by leukapheresis. An established BTSC line will be used as an allogeneic source of tumor antigen. Approximately 4 weeks will be required after the leukapheresis for vaccine production and the first vaccine administration.
Each patient will receive an injection of DCs at his/her assigned dose once every 2 weeks during the first 8 weeks, followed by injections every 4 weeks for an additional 10 vaccinations. Imiquimod will be applied to the vaccination site just prior to and 24 hours after each vaccine administration.
This study will use an accelerated dose escalation design (1 subject per level) until dose limiting toxicity (DLT) is encountered, after which a traditional phase I design (3 subjects per level) will be implemented. DLT is defined as grade 3 or greater treatment related toxicity. A total of 6 patients will be treated at the maximum tolerated dose (MTD) or, in the absence of DLT, at dose level 3.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Tumor, Glioblastoma, Medulloblastoma, Ependymoma, Anaplastic Astrocytoma
Keywords
Brain tumor, Immunotherapy, Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Level 3
Arm Type
Experimental
Arm Description
15 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
10 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
Arm Title
Dose Level 1
Arm Type
Experimental
Arm Description
5 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
Intervention Type
Biological
Intervention Name(s)
Dendritic Cells
Other Intervention Name(s)
DCs
Intervention Description
5, 10 or 15 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.
Intervention Type
Drug
Intervention Name(s)
Imiquimod
Other Intervention Name(s)
Aldara
Intervention Description
Imiquimod (INN) is a prescription medication that acts as an immune response modifier. Imiquimod is marketed as 5% Aldara cream in 250 mg packets, providing a total dose of 12.5 mg per packet and sufficient to cover 20 square centimeters. The contents of ½ of a packet will be applied as a thin film to cover approximately 10 square centimeters of skin in the area of the planned vaccination.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
To determine the safety and maximum tolerated dose (MTD) of dendritic cells (DCs) loaded with brain tumor stem cells (BTSCs) as a source of tumor antigen for immunotherapy in children and adults with recurrent GBM, ependymoma or medulloblastoma brain tumors. Toxicity is determined using the criteria established by the National Cancer Institute's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE).
Time Frame
4 Weeks Post Vaccination
Secondary Outcome Measure Information:
Title
Time to Tumor Progression
Description
To determine time to tumor progression in this patient population - exhibit a prolonged time to tumor progression by the absence of tumor growth as determined by MRI.
Time Frame
Every 4 Weeks From Baseline to 1 Year
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed brain tumors (glioblastoma multiforme, anaplastic astrocytoma, medullo
Age 0 through 17 years (pediatric subjects), and 18 years and above (adult subjects)
Lansky score of ≥ 60 (0-15 years) or Karnofsky (16 years or older) performance score of ≥ 60%
Adequate organ function within 14 days of study registration including the following:
Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0 x 10^9/L, platelets ≥100 x 10^9/L; hemoglobin ≥ 8 g/dL
Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
Renal: Normal serum creatinine for age (below) or creatinine clearance >60 ml/min/1.73 m^2.
Sexually active women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active men must agree to use barrier contraceptive for the duration of the vaccination period.
Willingness to travel to participate in study if from outside local region.
Voluntary written informed consent must be obtained from all patients (if of assent age) and their parents or legal guardians before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Exclusion criteria:
Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
Currently receiving any other investigational agents.
History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression).
Any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Moertel, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
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