Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

This study has been 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.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier:
NCT01403285
First received: July 21, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Drug: Cyclophosphamide
Biological: IMA950 plus GM-CSF
Biological: IMA950
Drug: Imiquimod
Phase 1

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by immatics Biotechnologies GmbH:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 6
Study Start Date: August 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01403285

Locations
United States, Maryland
Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
immatics Biotechnologies GmbH
Investigators
Principal Investigator: Teri Kreisl, MD Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD
  More Information

No publications provided

Responsible Party: immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier: NCT01403285     History of Changes
Obsolete Identifiers: NCT01386463
Other Study ID Numbers: IMA950-102, 11C0192
Study First Received: July 21, 2011
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by immatics Biotechnologies GmbH:
Glioblastoma
stable disease

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Imiquimod
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic
Interferon Inducers

ClinicalTrials.gov processed this record on August 28, 2014