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Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

Primary Purpose

Glioblastoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cyclophosphamide

IMA950 plus GM-CSF

IMA950

Imiquimod

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, stable disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health

Outcomes

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.

Number of AEs and percentage of patients with AEs (listed per grade and MedDRA preferred terms) will be reported.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01403285

First Posted

July 21, 2011

Last Updated

May 16, 2014

Sponsor

Immatics Biotechnologies GmbH

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01403285

Brief Title

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

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Terminated

Why Stopped

Due to poor accrual. This decision was taken without any safety reasons. Since beginning of the study (June 2011) only six patients were enrolled.

Study Start Date

August 2011 (undefined)

Primary Completion Date

April 2014 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Immatics Biotechnologies GmbH

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

Glioblastoma, stable disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

- Cytoxan (US name), - Endoxan (EU name)

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

IMA950 plus GM-CSF

Other Intervention Name(s)

- Granulocyte macrophage-colony stimulating factor, - Sargramostim, - Leukine

Intervention Description

Six vaccinations with IMA950 plus GM-CSF as adjuvant on 8 pre-defined days from Day 1 to Day 78

Intervention Type

Biological

Intervention Name(s)

IMA950

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Imiquimod

Other Intervention Name(s)

- Aldara

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Number of AEs and percentage of patients with AEs (listed per grade and MedDRA preferred terms) will be reported.

Time Frame

Continuously for up to 1 year plus follow-up

Title

Immunogenicity of IMA950

Description

Time Frame

6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)

Secondary Outcome Measure Information:

Title

Immune status parameters

Description

Time Frame

6 time points (blood drawings) during the first 3 months on study (pre-vaccination and during vaccination period)

Title

Biomarker assessment and correlation to clinical and immunological response

Description

Time Frame

Analysis time points are before the first vaccination and 15 weeks thereafter

Title

Clinical anti-tumor activity (response rate, 6-month progression-free survival)

Description

Clinical response rates, survival and progression-free survival (PFS) will be followed. PFS at 6 month will be reported.

Time Frame

Will be followed for 1 year (until end of study visit), overall survival will also be followed thereafter

Title

Influence of corticosteroids on immunogenicity of IMA950

Description

Time Frame

6 time points (blood drawings) during the first 3 months (pre- and post-vaccination)

Title

Health-related quality of life

Description

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.

Time Frame

Monthly for 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Teri Kreisl, MD

Organizational Affiliation

Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD

Official's Role

Principal Investigator

Facility Information:

Facility Name

Neuro-Oncology Branch of the National Cancer Institute, National Institutes of Health

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

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