- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01920191
Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Geneva, Switzerland, CH-1211
- Geneva University Hospitals, Centre of Oncology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IMA 950 and Poly ICLC
|
Other Names:
Blood samples, DTH analysis
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
up to 2 years
|
|
Overall survival (OS)
Time Frame: up to 2 years
|
up to 2 years
|
|
Immunologic endpoints
Time Frame: up to 2 years
|
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.
|
up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Pierre-Yves Dietrich, Professor, University Hospital, Geneva
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Nervous System Neoplasms
- Glioblastoma
- Central Nervous System Neoplasms
- Physiological Effects of Drugs
- Immunologic Factors
- Interferon Inducers
- Poly ICLC
Other Study ID Numbers
- IMA950 Poly ICLC
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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