Diffuse Intrinsic Pontine GliomaPhase 1NCT01400672
Imiquimod/Brain Tumor Initiating Cell (BTIC) Vaccine in Brain Stem Glioma
A Phase 1 study testing Tumor Lysate Vaccine, Imiquimod and Radiation therapy in people with Diffuse Intrinsic Pontine Glioma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
This is a pilot/feasibility study. The study design represents a modification of current standard of care for Diffuse Intrinsic Pontine Glioma (DIPG) (5580 cGY involved field radiation), with the final two doses of radiation given at intervals during the vaccination phase of treatment. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Tumor Lysate Vaccine, Imiquimod and Radiation therapy
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2012to 8 Oct 2018
- 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or older patients with histologically confirmed glioblastoma multiforme (GBM) World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy (enrollment plan 1).
- Age 3 years and older patients with diffuse intrinsic pontine glioma (DIPG) diagnosed by magnetic resonance imaging (MRI). Completion of standard radiation therapy (not to exceed 5580 cGy) with a post radiation therapy (RT) MRI that shows no disease progression when compared with pre-RT MRI. All patients must be treated with Intensity Modulated Radiation Therapy (IMRT) or an equivalent conformal technique. Patients from an outside institution who are referred after the start of radiation therapy may complete initial radiation therapy at their home institution as long as dosage guidelines are met and the total dose does not exceed 5580 cGy at the time of study registration (enrollment plan 2 and 3).
- all patients regardless of diagnosis must be clinically stable and off or on low dose (no more than 0.1 mg/kg/day, maximum of 4 mg/day dexamethasone) corticosteroid for at least 1 week prior to study enrollment.
Who cannot join
- Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days prior to 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 chemotherapy, investigational agents or registration on another therapy based trial or received chemotherapy with radiation therapy
- History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immunosuppression)
- Any isolated laboratory abnormality suggestive of a serious autoimmune disease
- Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
- Receiving ongoing treatment with immunosuppressive drugs, excluding those patients requiring dexamethasone for treatment of tumor-related edema
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: Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults
This is a pilot/feasibility study. The study design represents a modification of current standard of care for Diffuse Intrinsic Pontine Glioma (DIPG) (5580 cGY involved field radiation), with the final two doses of radiation given at intervals during the vaccination phase of treatment.
Patients between the ages of 3 years and 25 years diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) will be allowed to participate in the trial. Study enrollment will occur after the completion of conformal radiation therapy to a dose of 5580 cGy and the post radiation therapy (RT) magnetic resonance imaging (MRI) shows no disease progression.
Three patients with glioblastoma multiforme, aged 16 years and older, will be entered first to confirm vaccine safety before enrolling DIPG patients.
Read the detailed description
Vaccine will be produced by the University Of Minnesota Molecular and Cellular Therapeutics Facility using the established brain tumor initiating cell (BTIC) cell line GBM-6 as the antigen source. Vaccine administration will begin at four weeks (week 10) following completion of radiation therapy and will be given every two weeks for four doses. At the time of the 1st and 3rd vaccinations, additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5940 cGy. Subsequent vaccinations will be given every four weeks and will continue to a maximum of one year from study enrollment, by which time median survival will have passed based on historical data. Imaging will be obtained at study entry (post radiation therapy) and every eight weeks thereafter to eighteen months, after which time the interval between imaging follow-up episodes will be determined by the patient's clinical status. Imaging will include MRI of the brain using our current institutional brain tumor imaging protocol. Imaging will also include SPECT/MRI and perfusion MRI. FDG-PET imaging may be used in certain cases to differentiate tumor necrosis from progression.
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Being tested
- Tumor Lysate Vaccine, Imiquimod, Radiation therapy
- Keywords
- Diffuse intrinsic pontine glioma
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor Lysate VaccineBiological
Vaccination is injected intradermally every 2 weeks for 4 doses, then every 4 weeks for up to 1 year. Patients will receive 1 mg protein divided into 2 doses at two separate subinguinal sites.
ImiquimodDrug
Also called Aldara cream
Marketed as 5% Aldara cream topically applied; total of 12.5 mg divided between the two vaccination sites and reapplied at the vaccination sites 24 hours later.
Radiation therapyRadiation
Initial course of radiation therapy is given over 6-7 weeks, 5580 cGy. At the time of the 3rd vaccination, an additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5760 cGy.
| Study group | Role | What they receive |
|---|---|---|
| DIPG Patients Receiving Vaccine | Experimental | Patients with diffuse intrinsic pontine glioma (DIPG) receiving radiation therapy, Tumor Lysate Vaccine (dose of 4 x 10^6 cells divided into 2 doses then every 4 weeks for up to 1 year) and Imiquimod (5% Aldara cream at a total dose of 12.5 mg) topically at each site prior to and 24 hours after vaccination. Receives: Biological: Tumor Lysate Vaccine; Drug: Imiquimod; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity
Determined as Grade 3 or 4 toxicity observation after dosing with BTIC vaccination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0) in terms of local, regional and systemic events.
Measured: Within 24 hours of vaccination
Secondary outcomes (2)
Time to Tumor Progression
Imaging will include MRI, SPECT/MRI and perfusion MRI. FDG-PET imaging may be also be used Response criteria: Complete responses (CR) are those in which there is a disappearance of all enhancing tumor or tumor mass on consecutive MRI scans. Patients must be off steroids, and neurologically stable or improved.
Partial responses (PR) are those in which there is a ≥ 50% reduction in the size of the enhancing tumor or tumor mass on consecutive MRI scans. In addition, the patient must be neurologically stable.
Measured: Study entry through 24 months after treatment
Drop-out rate
Treatment feasibility will be based on the drop-out rate in absence of disease progression. Information will be presented in a tabular and descriptive manner
Measured: 24 hours, 48 hours and 1 week after each vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study start17 Jul 2012
- Primary completion7 Mar 2016
- Study completion8 Oct 2018
Why it stopped: Treatment ineffective; Extreme toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- 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
- Not applicable
- 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, M.D., Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01400672
- Sponsor's protocol ID
- 2009LS136
- Other IDs
- 1004M81213
- Status last verified
- Mar 2020
- First submitted
- 19 Jul 2011
- Last updated
- 18 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults
- ClinicalTrials.gov ID
- NCT01400672
- Acronym / sponsor ID
- 2009LS136
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Keywords
- Diffuse intrinsic pontine glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Treatment ineffective; Extreme toxicity
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 17 Jul 2012 (actual)
- Primary completion
- 7 Mar 2016 (actual)
- Study completion
- 8 Oct 2018 (actual)
- First posted
- 22 Jul 2011 (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 pilot/feasibility study. The study design represents a modification of current standard of care for Diffuse Intrinsic Pontine Glioma (DIPG) (5580 cGY involved field radiation), with the final two doses of radiation given at intervals during the vaccination phase of treatment.
Patients between the ages of 3 years and 25 years diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) will be allowed to participate in the trial. Study enrollment will occur after the completion of conformal radiation therapy to a dose of 5580 cGy and the post radiation therapy (RT) magnetic resonance imaging (MRI) shows no disease progression.
Three patients with glioblastoma multiforme, aged 16 years and older, will be entered first to confirm vaccine safety before enrolling DIPG patients.
Detailed description
Vaccine will be produced by the University Of Minnesota Molecular and Cellular Therapeutics Facility using the established brain tumor initiating cell (BTIC) cell line GBM-6 as the antigen source. Vaccine administration will begin at four weeks (week 10) following completion of radiation therapy and will be given every two weeks for four doses. At the time of the 1st and 3rd vaccinations, additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5940 cGy. Subsequent vaccinations will be given every four weeks and will continue to a maximum of one year from study enrollment, by which time median survival will have passed based on historical data. Imaging will be obtained at study entry (post radiation therapy) and every eight weeks thereafter to eighteen months, after which time the interval between imaging follow-up episodes will be determined by the patient's clinical status. Imaging will include MRI of the brain using our current institutional brain tumor imaging protocol. Imaging will also include SPECT/MRI and perfusion MRI. FDG-PET imaging may be used in certain cases to differentiate tumor necrosis from progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DIPG Patients Receiving Vaccine | Experimental | Biological: Tumor Lysate Vaccine, Drug: Imiquimod, Radiation: Radiation therapyPatients with diffuse intrinsic pontine glioma (DIPG) receiving radiation therapy, Tumor Lysate Vaccine (dose of 4 x 10^6 cells divided into 2 doses then every 4 weeks for up to 1 year) and Imiquimod (5% Aldara cream at a total dose of 12.5 mg) topically at each site prior to and 24 hours after vaccination. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Age 16 years or older patients with histologically confirmed glioblastoma multiforme (GBM) World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy (enrollment plan 1).
- Age 3 years and older patients with diffuse intrinsic pontine glioma (DIPG) diagnosed by magnetic resonance imaging (MRI). Completion of standard radiation therapy (not to exceed 5580 cGy) with a post radiation therapy (RT) MRI that shows no disease progression when compared with pre-RT MRI. All patients must be treated with Intensity Modulated Radiation Therapy (IMRT) or an equivalent conformal technique. Patients from an outside institution who are referred after the start of radiation therapy may complete initial radiation therapy at their home institution as long as dosage guidelines are met and the total dose does not exceed 5580 cGy at the time of study registration (enrollment plan 2 and 3).
- all patients regardless of diagnosis must be clinically stable and off or on low dose (no more than 0.1 mg/kg/day, maximum of 4 mg/day dexamethasone) corticosteroid for at least 1 week prior to study enrollment.
Key exclusion criteria (7 listed)
- Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days prior to 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 chemotherapy, investigational agents or registration on another therapy based trial or received chemotherapy with radiation therapy
- History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immunosuppression)
- Any isolated laboratory abnormality suggestive of a serious autoimmune disease
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 |
|---|---|---|
| Tumor Lysate VaccineVaccination is injected intradermally every 2 weeks for 4 doses, then every 4 weeks for up to 1 year. Patients will receive 1 mg protein divided into 2 doses at two separate subinguinal sites. | Biological | DIPG Patients Receiving Vaccine |
| ImiquimodAlso: Aldara creamMarketed as 5% Aldara cream topically applied; total of 12.5 mg divided between the two vaccination sites and reapplied at the vaccination sites 24 hours later. | Drug | DIPG Patients Receiving Vaccine |
| Radiation therapyInitial course of radiation therapy is given over 6-7 weeks, 5580 cGy. At the time of the 3rd vaccination, an additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5760 cGy. | Radiation | DIPG Patients Receiving Vaccine |
Primary outcome
Dose-limiting toxicity
Time frame: Within 24 hours of vaccination
Determined as Grade 3 or 4 toxicity observation after dosing with BTIC vaccination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0) in terms of local, regional and systemic events.
2 secondary outcomes
Time to Tumor Progression
Time frame: Study entry through 24 months after treatment
Drop-out rate
Time frame: 24 hours, 48 hours and 1 week after each vaccination
Results and safety
The study was stopped early (reason given: Treatment ineffective; Extreme toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2020.
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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, M.D. 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 Tumor Lysate Vaccine, Imiquimod and Radiation therapy in people with Diffuse Intrinsic Pontine Glioma, 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 3 inclusion and 7 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: stopped early, as of the sponsor's last update on 18 Mar 2020. 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 was stopped early (reason given: Treatment ineffective; Extreme toxicity). Results are not available in the source record.
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?
Dose-limiting toxicity (time frame: Within 24 hours of 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 18 Mar 2020.