GlioblastomaPhase 1Dendr2NCT04002804
Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Recurrence Of Glioblastoma Multiforme
A Phase 1 study testing Dendritic Cells Vaccine in people with Glioblastoma, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta.
Trial summary
Rationale of the Study: Treatment for GBM currently consists of surgical resection of the tumour mass followed by radio- and chemotherapy. Nonetheless overall prognosis still remains bleak, recurrence is universal, and recurrent GBM patients clearly need innovative therapies. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Dendritic Cells Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- No sites listed yet
- Study dates
- Apr 2010to 13 Jun 2017
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of both genders.
- Age 18 years and 70 years.
- Postoperative Karnofsky Performance Status >=70.
- Diagnosis of recurrent GBM (World Health Organization [WHO] grade IV astrocytoma).
- Diagnosis confirmed by the reference histopathology.
- Total or subtotal resection of tumor mass, confirmed by assessment of the neurosurgeon and by postoperative radiological assessment.
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- Amount of non-necrotic tissue for lysate preparation and DC loading >= 1 gr, stored at -80°C.
- Corticosteroids daily dose <= 4 mg during the 2 days prior to leukapheresis.
- Life expectancy > 3 months.
- Signed informed consent.
Who cannot join
- Pregnancy.
- Participation in other clinical trials with experimental drugs simultaneously or within 1 month before this trial entry.
- Presence of acute infection requiring active treatment.
- Mandatory treatment with corticosteroids or salicylates in anti-inflammatory dose.
- Presence of sub-ependymal diffusion of the tumor.
- Haematology: leukocytes < 3,000/μl, lymphocytes < 500/μl, neutrophils < 1,000/μl, hemoglobin <9 g/100 ml, thrombocytes < 100,000/μl 2 days prior to leukapheresis.
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- Documented immune deficiency.
- Documented autoimmune disease.
- Positive serology for HIV or hepatitis B or C.
- Allergies to any component of the DC vaccine.
- Known intolerance to TMZ.
- Other active malignancy.
About this study
Official title: Phase I Clinical Trial Of Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Recurrence Of Glioblastoma Multiforme
Rationale of the Study: Treatment for GBM currently consists of surgical resection of the tumour mass followed by radio- and chemotherapy. Nonetheless overall prognosis still remains bleak, recurrence is universal, and recurrent GBM patients clearly need innovative therapies. Dendritic cells (DC) immunotherapy could represent a well-tolerated, long-term tumour-specific treatment to kill all (residual) tumour cells which infiltrate in the adjacent areas of the brain. Preclinical investigations for the development of therapeutic vaccines against high grade gliomas, based on the use of DC loaded with a mixture of glioma-derived tumor have been carried out in rat as well as in mouse models, showing the capacity to generate a glioma-specific immune response. Mature DC loaded with autologous tumor lysate have been used also for the treatment of patients with recurrent malignant brain tumors; no major adverse events have been registered.
Results about the use of immunotherapy for GBM patients are encouraging, but further studies are necessary to find out the most effective and safe combination of immunotherapy with radio- and chemotherapy after exeresis of the tumour mass.
Read more
Aim of the study: Primary objective of the study is to evaluate treatment tolerability and to get preliminary information about efficacy. Secondary objective is to evaluate the treatment effect on the immune response. Additional objective is to identify a possible correlation between methylation status of the MGMT promoter and tumor response to treatment.
A two-stage Simon design will be considered for the study. The primary objectives of the study include the evaluation of a PFS6 rate in treated patients. Assuming as outcome measure the percentage of PFS6 patients and of clinical interest an increase to 35% (P1) of the historical control response rate of 20% (P0), the null hypothesis will be rejected (a=0.05, b=0.2) at the end of the first stage if the response rate will be 5/22 treated patients (Fisher's exact test). In the second stage patients will be enrolled up to 72 overall. The study will be successful if at least 19 subjects out of 72 have PFS6 months after the beginning of the treatment.
Read the detailed description
Study Design: Phase I, 2-stage Simon design (Simon et al., 1997), single-centre, un-controlled, open label, non randomized study.
The therapeutic program will include radical surgical resection of the tumor, followed by immunotherapy. Immunotherapy will comprise 4 biweekly vaccinations first (injections I, II, III, IV), 2 further monthly vaccinations (injections V, VI) and a final vaccination (injection VII) 2 months after the sixth one.
Injections I, V, VI and VII will contain 10 million tumor lysate-loaded DC, while the others will be of 5 million cells only. In correspondence to the third vaccine injection (week 7), 6 cycles of maintenance TMZ (mTMZ) will start. On the basis of the patient clinical status, further vaccine boosts will be considered as appropriate addition at the standard vaccination cycle.
Study Population: The first stage of the study will include 22 patients with recurrent GBM. The overall population at the end of the study will consist of 72 patients.
- Conditions
- Glioblastoma
- Being tested
- Dendritic Cells Vaccine
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic Cells VaccineBiological
Right after the surgical resection of the recurrent tumor, leukapheresis will be performed.
At least 5x109 PBMC must be collected by leukapheresis, so as to make the whole immunotherapy schedule workable.
Starting at week 3, immunotherapy will include 4 bi-weeekly vaccinations first (injections I, II, III, IV), two further monthly vaccinations (injections V, VI) and a final vaccination (injection VII) two months after the sixth one. Injections I, V, VI and VII will contain 10 million tumor lysate-loaded DC, while the others will be of 5 million cells only.
Vaccine doses will be injected in the forearm of the patient.
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy | Experimental | Autologous DC loaded with a autologous tumor lysate, in order to stimulate the immune response of the patient. Receives: Biological: Dendritic Cells Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Progression Free Survival at 6 Months (PFS-6)
PFS-6 is defined as the percentage of participants with PFS at 6 months from the date of surgery for tumor recurrence to the first date of objectively determined progressive disease based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010) or death from any cause. It is assumed that PFS follows an exponential distribution. Estimation using Kaplan-Meier analysis.
Measured: Baseline to 6 months
Secondary outcomes (2)
Incidence of Treatment-related Adverse Events
Tolerability will be assessed using CTCAE version 3.0 and recording incidence, severity and type of adverse events.
Measured: Tolerability will be monitored throughout study completion, an average of 2 months
Evaluation of the treatment effect on the immune response
Levels of regulatory and CD8+ T cell in treated patients
Measured: Immune response will be monitored throughout study completion, an average of 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2019
- Study startApr 2010
- Primary completionOct 2011
- Study completion13 Jun 2017
Why it stopped: Temozolomide does not favour immune response; secondary GBM to be excluded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe 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
- Model description
- Phase I, 2-stage Simon design (Simon et al., 1997), single-centre, un-controlled, open label, non randomized study.
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04002804
- Sponsor's protocol ID
- DENDR2
- Acronym
- Dendr2
- Status last verified
- Jun 2019
- First submitted
- 10 Jun 2019
- Last updated
- 1 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial Of Immunotherapy With Autologous Tumor Lysate-Loaded Dendritic Cells In Patients With Recurrence Of Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT04002804
- Acronym / sponsor ID
- Dendr2 / DENDR2
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Temozolomide does not favour immune response; secondary GBM to be excluded
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Study start
- Apr 2010 (actual)
- Primary completion
- Oct 2011 (actual)
- Study completion
- 13 Jun 2017 (actual)
- First posted
- 1 Jul 2019 (actual)
- 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.
Rationale of the Study: Treatment for GBM currently consists of surgical resection of the tumour mass followed by radio- and chemotherapy. Nonetheless overall prognosis still remains bleak, recurrence is universal, and recurrent GBM patients clearly need innovative therapies. Dendritic cells (DC) immunotherapy could represent a well-tolerated, long-term tumour-specific treatment to kill all (residual) tumour cells which infiltrate in the adjacent areas of the brain. Preclinical investigations for the development of therapeutic vaccines against high grade gliomas, based on the use of DC loaded with a mixture of glioma-derived tumor have been carried out in rat as well as in mouse models, showing the capacity to generate a glioma-specific immune response. Mature DC loaded with autologous tumor lysate have been used also for the treatment of patients with recurrent malignant brain tumors; no major adverse events have been registered.
Results about the use of immunotherapy for GBM patients are encouraging, but further studies are necessary to find out the most effective and safe combination of immunotherapy with radio- and chemotherapy after exeresis of the tumour mass.
Aim of the study: Primary objective of the study is to evaluate treatment tolerability and to get preliminary information about efficacy. Secondary objective is to evaluate the treatment effect on the immune response. Additional objective is to identify a possible correlation between methylation status of the MGMT promoter and tumor response to treatment.
A two-stage Simon design will be considered for the study. The primary objectives of the study include the evaluation of a PFS6 rate in treated patients. Assuming as outcome measure the percentage of PFS6 patients and of clinical interest an increase to 35% (P1) of the historical control response rate of 20% (P0), the null hypothesis will be rejected (a=0.05, b=0.2) at the end of the first stage if the response rate will be 5/22 treated patients (Fisher's exact test). In the second stage patients will be enrolled up to 72 overall. The study will be successful if at least 19 subjects out of 72 have PFS6 months after the beginning of the treatment.
Detailed description
Study Design: Phase I, 2-stage Simon design (Simon et al., 1997), single-centre, un-controlled, open label, non randomized study.
The therapeutic program will include radical surgical resection of the tumor, followed by immunotherapy. Immunotherapy will comprise 4 biweekly vaccinations first (injections I, II, III, IV), 2 further monthly vaccinations (injections V, VI) and a final vaccination (injection VII) 2 months after the sixth one.
Injections I, V, VI and VII will contain 10 million tumor lysate-loaded DC, while the others will be of 5 million cells only. In correspondence to the third vaccine injection (week 7), 6 cycles of maintenance TMZ (mTMZ) will start. On the basis of the patient clinical status, further vaccine boosts will be considered as appropriate addition at the standard vaccination cycle.
Study Population: The first stage of the study will include 22 patients with recurrent GBM. The overall population at the end of the study will consist of 72 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase I, 2-stage Simon design (Simon et al., 1997), single-centre, un-controlled, open label, non randomized study.
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy | Experimental | Biological: Dendritic Cells VaccineAutologous DC loaded with a autologous tumor lysate, in order to stimulate the immune response of the patient. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients of both genders.
- Age 18 years and 70 years.
- Postoperative Karnofsky Performance Status >=70.
- Diagnosis of recurrent GBM (World Health Organization [WHO] grade IV astrocytoma).
- Diagnosis confirmed by the reference histopathology.
Key exclusion criteria (12 listed)
- Pregnancy.
- Participation in other clinical trials with experimental drugs simultaneously or within 1 month before this trial entry.
- Presence of acute infection requiring active treatment.
- Mandatory treatment with corticosteroids or salicylates in anti-inflammatory dose.
- Presence of sub-ependymal diffusion of the tumor.
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 Cells VaccineRight after the surgical resection of the recurrent tumor, leukapheresis will be performed. At least 5x109 PBMC must be collected by leukapheresis, so as to make the whole immunotherapy schedule workable. Starting at week 3, immunotherapy will include 4 bi-weeekly vaccinations first (injections I, II, III, IV), two further monthly vaccinations (injections V, VI) and a final vaccination (injection VII) two months after the sixth one. Injections I, V, VI and VII will contain 10 million tumor lysate-loaded DC, while the others will be of 5 million cells only. Vaccine doses will be injected in the forearm of the patient. | Biological | Immunotherapy |
Primary outcome
Percentage of Participants With Progression Free Survival at 6 Months (PFS-6)
Time frame: Baseline to 6 months
PFS-6 is defined as the percentage of participants with PFS at 6 months from the date of surgery for tumor recurrence to the first date of objectively determined progressive disease based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010) or death from any cause. It is assumed that PFS follows an exponential distribution. Estimation using Kaplan-Meier analysis.
2 secondary outcomes
Incidence of Treatment-related Adverse Events
Time frame: Tolerability will be monitored throughout study completion, an average of 2 months
Evaluation of the treatment effect on the immune response
Time frame: Immune response will be monitored throughout study completion, an average of 2 months
Results and safety
The study was stopped early (reason given: Temozolomide does not favour immune response; secondary GBM to be excluded). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dendritic Cells Vaccine in people with Glioblastoma, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta.
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 12 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 1 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
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: Temozolomide does not favour immune response; secondary GBM to be excluded). 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?
Percentage of Participants With Progression Free Survival at 6 Months (PFS-6) (time frame: Baseline to 6 months). 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 1 Jul 2019.