Clinical trial NCT01403285: Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma
Official title: A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Glioblastoma
Keywords: Glioblastoma
stable disease
Lead sponsor: Immatics Biotechnologies GmbH
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-07-27
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Continuously for up to 1 year plus follow-up
measure: Immunogenicity of IMA950
timeFrame: 6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)
Secondary outcomes:
measure: Immune status parameters
timeFrame: 6 time points (blood drawings) during the first 3 months on study (pre-vaccination and during vaccination period)
measure: Biomarker assessment and correlation to clinical and immunological response
timeFrame: Analysis time points are before the first vaccination and 15 weeks thereafter
measure: Clinical anti-tumor activity (response rate, 6-month progression-free survival)
timeFrame: Will be followed for 1 year (until end of study visit), overall survival will also be followed thereafter
measure: Influence of corticosteroids on immunogenicity of IMA950
timeFrame: 6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)
measure: Health-related quality of life
timeFrame: Monthly for 1 year
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health
state: Maryland
Study officials:
affiliation: Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD
name: Teri Kreisl, MD
role: PRINCIPAL_INVESTIGATOR
References: