Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)

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.

Study Overview

• Status: Terminated
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Cyclophosphamide; Biological: IMA950 plus GM-CSF; Biological: IMA950; Drug: Imiquimod

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Number of AEs and percentage of patients with AEs (listed per grade and MedDRA preferred terms) will be reported.	Continuously for up to 1 year plus follow-up
Immunogenicity of IMA950	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.	6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune status parameters	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.	6 time points (blood drawings) during the first 3 months on study (pre-vaccination and during vaccination period)
Biomarker assessment and correlation to clinical and immunological response	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.	Analysis time points are before the first vaccination and 15 weeks thereafter
Clinical anti-tumor activity (response rate, 6-month progression-free survival)	Clinical response rates, survival and progression-free survival (PFS) will be followed. PFS at 6 month will be reported.	Will be followed for 1 year (until end of study visit), overall survival will also be followed thereafter
Influence of corticosteroids on immunogenicity of IMA950	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.	6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)
Health-related quality of life	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.	Monthly for 1 year

Collaborators and Investigators

• Sponsor: Immatics Biotechnologies GmbH
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Teri Kreisl, MD, Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 26, 2011
• First Posted (Estimate): July 27, 2011

Study Record Updates

• Last Update Posted (Estimate): May 19, 2014
• Last Update Submitted That Met QC Criteria: May 16, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Glioblastoma; stable disease
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Adjuvants, Immunologic; Interferon Inducers; Cyclophosphamide; Imiquimod; Sargramostim; Molgramostim
• Other Study ID Numbers: IMA950-102; 11C0192 (Other Identifier: National Cancer Institute)