Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma - Full Text View

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:

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Imiquimod Sargramostim

U.S. FDA Resources

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.

Estimated Enrollment:	25
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)

Intervention Details:

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)

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

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

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

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

Contacts

Contact: Joohee Sul, MD

301-402-6298

Locations

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

Sponsors and Collaborators

immatics Biotechnologies GmbH

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Joohee Sul, 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 8, 2013
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 June 17, 2013