CNS Tumor, AdultPhase 1/2NCT01920191
Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma
A Phase 1/2 study testing IMA 950, Poly ICLC and Immunomonitoring in people with CNS Tumor, Adult, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CNS Tumor, Adult
- What is being tested?
- IMA 950, Poly ICLC and Immunomonitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteSwitzerland
- Study dates
- Aug 2013to Mar 2016
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological documentation of glioblastoma. For experimental purposes only, 5 additional grade III astrocytoma may be included (these cases will not be included in the endpoints analysis).
- Patients must have completed radiation therapy with concomitant temozolomide.
- HLA-A2 positive.
- Eastern Cooperative Oncology Group performance status of 0 or 1 (Appendix1).
- Age > 18 years, life expectancy of least 4 months.
- Patient must be on stable or decreasing dose of steroids, with a maximal dose of Dexamethasone of 4mg/day.
Show all 9Show fewer
- Adequate bone marrow, liver and kidney function.
- Hepatitis B serology negative (HBcAg-seronegative)
- Written (signed and dated) informed consent. Capable of co-operating with standard therapy and IMA950 with Poly-ICLC vaccinations and follow-up.
Who cannot join
- Any other vaccination given within 2 weeks before first IMA950 vaccination.
- History of cardiac disease: congestive heart failure > New York heart association class 2, active CAD, cardiac requiring anti-arrhythmic therapy or uncontrolled hypertension.
- History of HIV infection or chronic hepatitis B or C or clinical active infections.
- Patients with evidence of history bleeding diathesis.
- Pregnant or potentially pregnant patients. Women of childbearing age must be tested for pregnancy (serum or urine HCG) before treatment and must not contemplate pregnancy during the study
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Geneva University Hospitals, Centre of Oncology
Geneva, CH-1211
About this study
Official title: Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients
RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.
Read the detailed description
OBJECTIVES
Primary
- Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0.
- Immunogenicity of IMA950 plus Poly-ICLC when given together with temozolomide.
Secondary
- 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
- Overall survival (OS)
- Immunologic endpoints (correlation between clinical and immunological responses):
- evaluation of peptide immunogenicity by tetramer staining
- analysis of memory, activation and homing marker expression by tetramer positive cells
- analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
- analysis of the presence of T regulatory and myeloid-derived suppressor cells
- The immunological analyses will be performed on:
- peripheral blood mononuclear cells (PBMC)
- cultures of skin punch biopsy at delayed-type hypersensitivity (DTH) site
- tumor-infiltrating lymphocytes (TIL) if brain tissue is available at recurrence
OUTLINE
This is a monocentric, open label, one cohort, safety and immunogenicity, Phase I/II study.
A maximum of 16 HLA-A2 positive patients with newly diagnosed glioblastoma will be enrolled into the study after treatment with radiation therapy and concurrent temozolomide.
All patients will receive the same dose of IMA950 with Poly-ICLC and follow the same vaccination schedule which comprises a Vaccination Induction Phase of 4 intensive vaccinations, followed by a Vaccination Maintenance Phase of five vaccinations over a longer period.
The Vaccination Induction Phase will start a minimum of 7 days after the final radiotherapy/TMZ dose of CRT and 28 days (+7 days) prior to the first scheduled dose of adjuvant TMZ.
This will ensure that all 4 vaccinations in the Induction Phase will be administered a week after immunosuppressive therapy (i.e. combined radiotherapy and temozolomide) and will finish a week prior to the start of adjuvant TMZ.
Two Phases :
Induction phase, patient receive the first 4 doses of Poly ICLC mixed with IMA 950 Peptide based vaccine (subcutaneously or IM) on days 1,8,15, and 21 in absence of unacceptable toxicity or disease progression.
Maintenance Phase, patient receive Poly ICLC mixed with IMA 950 Peptide based vaccine (SC or IM) on day 21 of each adjuvant temozolomide cycle in absence unacceptable toxicity or disease progression.
Immunomonitoring assessments will be performed at 8 time points with blood samples collection and one DTH site analysis(after vaccination 5).
Brain MRI will be performed every two months for disease assessment.
N.B. :
An amendment has been accepted by Swissmedic and Local Ethics committee on september 2014, after suboptimal immunomonitoring preliminary assessments, the schedule of administration has been changed in order to improve the immunogenicity of the vaccine, as follows :
- injection of mixed peptides and adjuvant Poly ICLC
- 4 vaccinations in the induction phase instead of 6
- one site of injection (thigh)
- two arms for the next 10 patients to be included that will be equally divided in 2 groups : one group will be vaccinated subcutaneously and the other intramuscularly.
- Conditions
- CNS Tumor, Adult
- Being tested
- IMA 950, Poly ICLC, Immunomonitoring
- Keywords
- Glioblastoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMA 950Biological
Poly ICLCBiological
Also called Hiltonol
ImmunomonitoringOther
Blood samples, DTH analysis
| Study group | Role | What they receive |
|---|---|---|
| IMA 950 and Poly ICLC | Experimental | Not described Receives: Biological: IMA 950; Biological: Poly ICLC; Other: Immunomonitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0
Measured: up to 2 years
Secondary outcomes (3)
6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
Measured: up to 2 years
Overall survival (OS)
Measured: up to 2 years
Immunologic endpoints
Correlation between clinical and immunological response. Blood sampling at baseline (week 4 and 5 after beginning of radiotherapy with concomitant temozolomide) and at week 10,11,12,16,19,23,27 and 31.
Punch biopsy at DTH (Delayed Type Hypersensitivity) site performed 48h after DTH skin test 7 days after Vaccination 7.
- evaluation of peptide immunogenicity by tetramer staining
- analysis of memory, activation and homing marker expression by tetramer positive cells
- analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
- analysis of the presence of T regulatory and myeloid-derived suppressor cells
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2013 (estimated)
- Study startAug 2013
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CNS Tumor, AdultStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- Immatics Biotechnologies GmbH, Oncovir, Inc.
- Responsible party
- Principal investigator, Pierre-Yves Dietrich, University Hospital, Geneva
- Investigators
- Pierre-Yves Dietrich, Professor, Principal investigator, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01920191
- Sponsor's protocol ID
- IMA950 Poly ICLC
- Status last verified
- Apr 2016
- First submitted
- 31 Jul 2013
- Last updated
- 20 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Migliorini D, Dutoit V, Allard M, Grandjean Hallez N, Marinari E, Widmer V, Philippin G, Corlazzoli F, Gustave R, Kreutzfeldt M, Blazek N, Wasem J, Hottinger A, Koka A, Momjian S, Lobrinus A, Merkler D, Vargas MI, Walker PR, Patrikidou A, Dietrich PY. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncol. 2019 Jul 11;21(7):923-933. doi: 10.1093/neuonc/noz040.
PubMed 30753611
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients
- ClinicalTrials.gov ID
- NCT01920191
- Acronym / sponsor ID
- IMA950 Poly ICLC
- Conditions
- CNS Tumor, Adult
- Keywords
- Glioblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- Immatics Biotechnologies GmbH, Oncovir, Inc.
- Study start
- Aug 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 9 Aug 2013 (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.
RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.
Detailed description
OBJECTIVES
Primary
- Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0.
- Immunogenicity of IMA950 plus Poly-ICLC when given together with temozolomide.
Secondary
- 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
- Overall survival (OS)
- Immunologic endpoints (correlation between clinical and immunological responses):
- evaluation of peptide immunogenicity by tetramer staining
- analysis of memory, activation and homing marker expression by tetramer positive cells
- analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
- analysis of the presence of T regulatory and myeloid-derived suppressor cells
- The immunological analyses will be performed on:
- peripheral blood mononuclear cells (PBMC)
- cultures of skin punch biopsy at delayed-type hypersensitivity (DTH) site
- tumor-infiltrating lymphocytes (TIL) if brain tissue is available at recurrence
OUTLINE
This is a monocentric, open label, one cohort, safety and immunogenicity, Phase I/II study.
A maximum of 16 HLA-A2 positive patients with newly diagnosed glioblastoma will be enrolled into the study after treatment with radiation therapy and concurrent temozolomide.
All patients will receive the same dose of IMA950 with Poly-ICLC and follow the same vaccination schedule which comprises a Vaccination Induction Phase of 4 intensive vaccinations, followed by a Vaccination Maintenance Phase of five vaccinations over a longer period.
The Vaccination Induction Phase will start a minimum of 7 days after the final radiotherapy/TMZ dose of CRT and 28 days (+7 days) prior to the first scheduled dose of adjuvant TMZ.
This will ensure that all 4 vaccinations in the Induction Phase will be administered a week after immunosuppressive therapy (i.e. combined radiotherapy and temozolomide) and will finish a week prior to the start of adjuvant TMZ.
Two Phases :
Induction phase, patient receive the first 4 doses of Poly ICLC mixed with IMA 950 Peptide based vaccine (subcutaneously or IM) on days 1,8,15, and 21 in absence of unacceptable toxicity or disease progression.
Maintenance Phase, patient receive Poly ICLC mixed with IMA 950 Peptide based vaccine (SC or IM) on day 21 of each adjuvant temozolomide cycle in absence unacceptable toxicity or disease progression.
Immunomonitoring assessments will be performed at 8 time points with blood samples collection and one DTH site analysis(after vaccination 5).
Brain MRI will be performed every two months for disease assessment.
N.B. :
An amendment has been accepted by Swissmedic and Local Ethics committee on september 2014, after suboptimal immunomonitoring preliminary assessments, the schedule of administration has been changed in order to improve the immunogenicity of the vaccine, as follows :
- injection of mixed peptides and adjuvant Poly ICLC
- 4 vaccinations in the induction phase instead of 6
- one site of injection (thigh)
- two arms for the next 10 patients to be included that will be equally divided in 2 groups : one group will be vaccinated subcutaneously and the other intramuscularly.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMA 950 and Poly ICLC | Experimental | Biological: IMA 950, Biological: Poly ICLC, Other: Immunomonitoring |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histological documentation of glioblastoma. For experimental purposes only, 5 additional grade III astrocytoma may be included (these cases will not be included in the endpoints analysis).
- Patients must have completed radiation therapy with concomitant temozolomide.
- HLA-A2 positive.
- Eastern Cooperative Oncology Group performance status of 0 or 1 (Appendix1).
- Age > 18 years, life expectancy of least 4 months.
Key exclusion criteria (5 listed)
- Any other vaccination given within 2 weeks before first IMA950 vaccination.
- History of cardiac disease: congestive heart failure > New York heart association class 2, active CAD, cardiac requiring anti-arrhythmic therapy or uncontrolled hypertension.
- History of HIV infection or chronic hepatitis B or C or clinical active infections.
- Patients with evidence of history bleeding diathesis.
- Pregnant or potentially pregnant patients. Women of childbearing age must be tested for pregnancy (serum or urine HCG) before treatment and must not contemplate pregnancy during the study
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 |
|---|---|---|
| IMA 950 | Biological | IMA 950 and Poly ICLC |
| Poly ICLCAlso: Hiltonol | Biological | IMA 950 and Poly ICLC |
| ImmunomonitoringBlood samples, DTH analysis | Other | IMA 950 and Poly ICLC |
Primary outcome
Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0
Time frame: up to 2 years
3 secondary outcomes
6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
Time frame: up to 2 years
Overall survival (OS)
Time frame: up to 2 years
Immunologic endpoints
Time frame: up to 2 years
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 20 Apr 2016.
- Derived from this study: PubMed 30753611Migliorini D, Dutoit V, Allard M, Grandjean Hallez N, Marinari E, Widmer V, Philippin G, Corlazzoli F, Gustave R, Kreutzfeldt M, Blazek N, Wasem J, Hottinger A, Koka A, Momjian S, Lobrinus A, Merkler D, Vargas MI, Walker PR, Patrikidou A, Dietrich PY. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncol. 2019 Jul 11;21(7):923-933. doi: 10.1093/neuonc/noz040.
Related trials for CNS Tumor, Adult
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Recruiting
Virtual Home-based Exercise Intervention (RISE) to Improve Cancer-Related Cognitive Impairment and Gut Microbiome in Adolescent and Young Adult Brain Tumor Survivors
Cancer-related Cognitive Dysfunction, Primary Brain Neoplasm
RecruitingPhase 2
A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma
Lymphoma
Active, not recruitingPhase 1/2
Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
Solid Tumor, Central Nervous System Tumor
Active, not recruitingPhase 1
ADAGiO: Adoptive Cellular Therapy for the TreAtment of Recurrent OliGodendrogliOma (OG) Adult Patients
Recurrent Oligodendroglioma, Progressive Oligodendroglioma
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.
Pierre-Yves Dietrich, Professor principal investigator
University Hospital, Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IMA 950, Poly ICLC and Immunomonitoring in people with CNS Tumor, Adult, run by University Hospital, Geneva at 1 site in Switzerland.
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 9 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 20 Apr 2016. 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 Switzerland. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0 (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01920191, which also lists 1 linked publication.
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 20 Apr 2016.