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Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

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ClinicalTrials.gov Identifier: NCT01403285
Recruitment Status : Terminated (Due to poor accrual. This decision was taken without any safety reasons. Since beginning of the study (June 2011) only six patients were enrolled.)
First Posted : July 27, 2011
Last Update Posted : May 19, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
immatics Biotechnologies GmbH

Tracking Information
First Submitted Date  ICMJE July 21, 2011
First Posted Date  ICMJE July 27, 2011
Last Update Posted Date May 19, 2014
Study Start Date  ICMJE August 2011
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2011)
  • 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 ]
    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) ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2011)
  • Immune status parameters [ Time Frame: 6 time points (blood drawings) during the first 3 months on study (pre-vaccination and during vaccination period) ]
    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 ]
    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 ]
    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) ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma
Official Title  ICMJE A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: Cyclophosphamide
    One single low-dose i.v. infusion of cyclophosphamide (300mg/m2) prior to the first vaccination as pre-treatment
    Other Names:
    • - Cytoxan (US name)
    • - Endoxan (EU name)
  • Biological: IMA950 plus GM-CSF
    Six vaccinations with IMA950 plus GM-CSF as adjuvant on 8 pre-defined days from Day 1 to Day 78
    Other Names:
    • - Granulocyte macrophage-colony stimulating factor
    • - Sargramostim
    • - Leukine
  • Biological: IMA950
    After Day 78, vaccinations with IMA950 (no GM-CSF) will be given on a monthly basis for up to one year from start of vaccination or until disease progression
  • Drug: Imiquimod
    Imiquimod will be topically applied 10-20 minutes after each vaccination. After the third vaccination onward patients will apply additional imiquimod 24 hours after each vaccination at home on their own
    Other Name: - Aldara
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 14, 2014)
6
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2011)
25
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically proven glioblastoma
  • Stable disease following ≥ 4 cycles of adjuvant temozolomide
  • No progression or recurrence of disease

PATIENT CHARACTERISTICS:

  • HLA-A*02 positive
  • ≥ 18 years old
  • Life expectancy > 8 weeks
  • Karnofsky performance status ≥ 60
  • WBC >3,500/µL
  • ALC >350/mm3
  • ANC >1,500/mm3
  • Platelet count >100,000/mm3
  • Hemoglobin >10gm/dL
  • AST, ALT and alkaline phosphatase <2.5 times upper limit of normal (ULN)
  • Bilirubin <1.5 times ULN
  • Creatinine <1.5 mg/dL and/or creatinine clearance >60cc/min
  • Serum potassium, magnesium and calcium within normals levels (supplementation is allowed)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Practice birth control during and for 2 months after treatment with IMA950 (both genders)
  • Women of childbearing age must agree to use adequate contraceptive methods
  • No significant active hepatic, renal, infectious or psychiatric disease
  • No HIV, active hepatitis infection, or any other active severe infectious disease
  • No history of autoimmune disease or immunosuppression
  • No clinically significant cardiovascular event within 3 months before study entry or an increased risk for ventricular arrhythmia
  • No malignancy other than glioblastoma that required treatment during the last 12 months

PRIOR and/or CONCURRENT THERAPY:

  • See Disease Characteristics
  • Completed radiotherapy and at least 4 cycles of adjuvant temozolomide
  • Not be receiving steroids OR be on stable dose of steroids for ≥ 5 days prior to registration
  • No other prior immunotherapy for glioblastoma
  • No major surgery within 4 weeks prior to treatment start
  • At least 4 weeks from cytotoxic therapies (incl. temozolomide)
  • At least 2 weeks from non-cytotoxic therapies (e.g. interferon, tamoxifen)
  • At least 3 weeks from bevacizumab
  • No current treatment with imiquimod; prior use of imiquimod is allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01403285
Other Study ID Numbers  ICMJE IMA950-102
11C0192 ( Other Identifier: National Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party immatics Biotechnologies GmbH
Study Sponsor  ICMJE immatics Biotechnologies GmbH
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Teri Kreisl, MD Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD
PRS Account immatics Biotechnologies GmbH
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP