Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

NCT01403285 | Terminated Phase 1 DMC

• 2 other identifiers: IMA950-10211C0192
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Keywords

Glioblastoma; stable disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Immune status parameters

  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

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

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

  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

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

• Health-related quality of life

  Monthly for 1 year

Interventions

Cyclophosphamide DRUG

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

Also known as: - Cytoxan (US name), - Endoxan (EU name)

IMA950 plus GM-CSF BIOLOGICAL

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

Also known as: - Granulocyte macrophage-colony stimulating factor, - Sargramostim, - Leukine

IMA950 BIOLOGICAL

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 DRUG

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

Also known as: - Aldara

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Immatics Biotechnologies GmbH: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

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

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Cyclophosphamide; IMA950; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; sargramostim; Imiquimod

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Teri Kreisl, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2011
• First Posted: July 27, 2011
• Study Start: August 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 19, 2014

Record last verified: 2014-05

Locations

US (1)