Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma
BACKGROUND: Active immunotherapy of cancer is based on the premise that the vaccine raises a cytotoxic immune response to tumor-associated antigens, thereby destroying malignant cells without harming normal cells.
IMA950 is a therapeutic multi-peptide vaccine containing 11 tumor-associated peptides (TUMAPs) found in a majority of glioblastomas, and is designed to activate TUMAP-specific T cells. The use of 11 TUMAPs increases the likelihood of a multi-clonal, highly specific T-cell response against tumor cells leading to decreased likelihood of immune evasion of the tumor by down-regulation of target antigens.
PURPOSE: The primary objective of this study is to determine the safety and tolerability of IMA950 when given with cyclophosphamide, granulocyte macrophage-colony stimulating factor (GM-CSF) and imiquimod in patients with glioblastoma and to determine if IMA950 shows sufficient immunogenicity in these patients.
ELIGIBILITY: Patients with histologically proven GBMs who have completed radiotherapy, and have stable disease following at least 4 cycles of adjuvant temozolomide.
Biological: IMA950 plus GM-CSF
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)|
- Safety and tolerability of IMA950 administered with granulocyte macrophage colony stimulating factor (GM-CSF) and topical imiquimod together following a single low-dose application of cyclophosphamide. [ Time Frame: Continuously for up to 1 year plus follow-up ] [ Designated as safety issue: Yes ]Number of AEs and percentage of patients with AEs (listed per grade and MedDRA preferred terms) will be reported.
- Immunogenicity of IMA950 [ Time Frame: 6 time points (blood drawings) during the first 3 months (pre- and post-vaccination) ] [ Designated as safety issue: No ]Vaccine-induced immune responses to peptides contained in IMA950 will be measured by multimer assay using peripheral blood. Percentage of immune responders (patients with at least one vaccine-induced immune response to IMA950 peptides) and percentage of multi-TUMAP responders (patients with vaccine-induced immune responses to ≥2 peptides in IMA950) will be reported.
- Immune status parameters [ Time Frame: 6 time points (blood drawings) during the first 3 months on study (pre-vaccination and during vaccination period) ] [ Designated as safety issue: No ]Relative frequencies and absolute numbers per µl blood of regulatory T-cells and (if sufficient cells are available) other immune cell populations will be measured from peripheral blood. Focus is on analysis of pre-vaccination frequencies.
- Biomarker assessment and correlation to clinical and immunological response [ Time Frame: Analysis time points are before the first vaccination and 15 weeks thereafter ] [ Designated as safety issue: No ]Serum levels of proteins and other factors that are indicative of the immune status of the patients will be measured (e.g TGF-beta) and will be correlated with immune response rates and clinical outcome.
- Clinical anti-tumor activity (response rate, 6-month progression-free survival) [ Time Frame: Will be followed for 1 year (until end of study visit), overall survival will also be followed thereafter ] [ Designated as safety issue: No ]Clinical response rates, survival and progression-free survival (PFS) will be followed. PFS at 6 month will be reported.
- Influence of corticosteroids on immunogenicity of IMA950 [ Time Frame: 6 time points (blood drawings) during the first 3 months (pre- and post-vaccination) ] [ Designated as safety issue: No ]Corticosteroid levels are not limited in this trial. It will descriptively reported whether the known immunosuppressive effects of corticosteroids are reflected in different immune response rates for patients treated or not treated with corticosteroids.
- Health-related quality of life [ Time Frame: Monthly for 1 year ] [ Designated as safety issue: No ]FACT-Br(4.0) questionnaire will be used to assess HRQL. HRQL scores (total, Trial Outcome Index, subscales) will be reported at baseline. Changes from baseline will also be evaluated.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
- - Cytoxan (US name)
- - Endoxan (EU name)
- - Granulocyte macrophage-colony stimulating factor
- - Sargramostim
- - Leukine
|Contact: Joohee Sul, MD||301-402-6298|
|United States, Maryland|
|Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Joohee Sul, MD 301-402-6298|
|Principal Investigator: Joohee Sul, MD|
|Principal Investigator:||Joohee Sul, MD||Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD|