Brain TumorPhase 1NCT01171469
Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
A Phase 1 study testing Dendritic Cells and Imiquimod in people with Brain Tumor and Glioblastoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Brain Tumor, Glioblastoma, Medulloblastoma
- What is being tested?
- Dendritic Cells and Imiquimod
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Phase I Study of Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Recurrent or Progressive Malignant Gliomas
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.
Read the 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.
- Conditions
- Brain Tumor, Glioblastoma, Medulloblastoma, Ependymoma, Anaplastic Astrocytoma
- Being tested
- Dendritic Cells, Imiquimod
- Keywords
- Brain tumor, Immunotherapy, Glioma
- Medical subject headings
- Brain Neoplasms, Glioblastoma, Medulloblastoma, Ependymoma, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic CellsBiological
Also called DCs
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.
ImiquimodDrug
Also called Aldara
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 3 | Experimental | 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. Receives: Biological: Dendritic Cells; Drug: Imiquimod |
| Dose Level 2 | Experimental | 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. Receives: Biological: Dendritic Cells; Drug: Imiquimod |
| Dose Level 1 | Experimental | 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. Receives: Biological: Dendritic Cells; Drug: Imiquimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 Weeks Post Vaccination
Secondary outcomes (1)
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.
Measured: Every 4 Weeks From Baseline to 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2010 (estimated)
- Study startSep 2010
- Primary completionMay 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher Moertel, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01171469
- Sponsor's protocol ID
- 2008LS053
- Other IDs
- 0809M48641
- Status last verified
- Nov 2017
- First submitted
- 27 Jul 2010
- Last updated
- 2 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Recurrent or Progressive Malignant Gliomas
- ClinicalTrials.gov ID
- NCT01171469
- Acronym / sponsor ID
- 2008LS053
- Conditions
- Brain Tumor, Glioblastoma, Medulloblastoma, Ependymoma, Anaplastic Astrocytoma
- Keywords
- Brain tumor, Immunotherapy, Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- May 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 28 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 3 | Experimental | Biological: Dendritic Cells, Drug: Imiquimod15 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. |
| Dose Level 2 | Experimental | Biological: Dendritic Cells, Drug: Imiquimod10 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. |
| Dose Level 1 | Experimental | Biological: Dendritic Cells, Drug: Imiquimod5 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dendritic CellsAlso: DCs5, 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. | Biological | Dose Level 1, Dose Level 2, Dose Level 3 |
| ImiquimodAlso: AldaraImiquimod (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. | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
Maximum Tolerated Dose
Time frame: 4 Weeks Post Vaccination
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).
1 secondary outcome
Time to Tumor Progression
Time frame: Every 4 Weeks From Baseline to 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Moertel, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dendritic Cells and Imiquimod in people with Brain Tumor and Glioblastoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 4 Weeks Post Vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.