Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma
Primary Purpose
CNS Tumor, Adult
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
IMA 950
Poly ICLC
Immunomonitoring
Sponsored by
About this trial
This is an interventional treatment trial for CNS Tumor, Adult focused on measuring Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Geneva University Hospitals, Centre of Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IMA 950 and Poly ICLC
Arm Description
Outcomes
Primary Outcome Measures
Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0
Secondary Outcome Measures
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 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
Full Information
NCT ID
NCT01920191
First Posted
July 31, 2013
Last Updated
April 19, 2016
Sponsor
University Hospital, Geneva
Collaborators
Immatics Biotechnologies GmbH, Oncovir, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01920191
Brief Title
Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Geneva
Collaborators
Immatics Biotechnologies GmbH, Oncovir, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CNS Tumor, Adult
Keywords
Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IMA 950 and Poly ICLC
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
IMA 950
Intervention Type
Biological
Intervention Name(s)
Poly ICLC
Other Intervention Name(s)
Hiltonol
Intervention Type
Other
Intervention Name(s)
Immunomonitoring
Intervention Description
Blood samples, DTH analysis
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Overall survival (OS)
Time Frame
up to 2 years
Title
Immunologic endpoints
Description
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
Time Frame
up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre-Yves Dietrich, Professor
Organizational Affiliation
University Hospital, Geneva
Official's Role
Principal Investigator
Facility Information:
Facility Name
Geneva University Hospitals, Centre of Oncology
City
Geneva
ZIP/Postal Code
CH-1211
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
30753611
Citation
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.
Results Reference
derived
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Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma
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