Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01403285
• Other study ID #: IMA950-102
• Secondary ID: 11C0192
• Status: Terminated
• Phase: Phase 1
• First received: July 21, 2011
• Last updated: May 16, 2014
• Start date: August 2011
• Est. completion date: April 2014

Study information

• Verified date: May 2014
• Source: immatics Biotechnologies GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT01386463

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Cyclophosphamide
One single low-dose i.v. infusion of cyclophosphamide (300mg/m2) prior to the first vaccination as pre-treatment

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
• 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

Locations

Country	Name	City	State
United States	Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
immatics Biotechnologies GmbH	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No