Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT00643097 | Completed Phase 2 Results DMC

• 4 other identifiers: Pro00004040P50NS020023CDR0000589632DUMC-5421
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Vaccines made from a peptide may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with newly diagnosed glioblastoma multiforme.

Conditions

Malignant Neoplasms of Brain

Keywords

adult giant cell glioblastoma; adult gliosarcoma; adult glioblastoma

Outcome Measures

Primary Outcomes (2)

• Humoral and Cellular Immune Response

  Number of patients that developed a delayed-type hypersensitivity (DTH) response at following vaccination. Any skin reaction in response to the intradermal injection of the antigen was measured and recorded. A positive skin test was defined as \> 5 mm induration (swelling).

  26 months

• Clinical Efficacy of Vaccination, in Terms of Progression-free Survival (PFS)

  Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).

  58 months

Secondary Outcomes (2)

• Response to Vaccination

  26 months

• Toxicity to PEP-3 Vaccine Immunization

  26 months

Study Arms (3)

Arm I (ACTIVATE)

EXPERIMENTAL

Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)-specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF), referred to as PEP-3 vaccine, every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.

Biological: PEP-3 vaccine; Biological: sargramostim; Drug: Temozolomide

Arm II (ACT II STD)

EXPERIMENTAL

Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF), referred to as PEP-3 vaccine, biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.

Biological: PEP-3 vaccine; Biological: sargramostim; Drug: Temozolomide

Arm III (ACT II DI)

EXPERIMENTAL

Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF), referred to as PEP-3 vaccine, biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.

Biological: PEP-3 vaccine; Biological: sargramostim; Drug: Temozolomide

Interventions

PEP-3 vaccine BIOLOGICAL

Given intradermally

Arm I (ACTIVATE); Arm II (ACT II STD); Arm III (ACT II DI)

sargramostim BIOLOGICAL

Given intradermally

Arm I (ACTIVATE); Arm II (ACT II STD); Arm III (ACT II DI)

Temozolomide DRUG

Standard of care chemotherapy

Also known as: TMZ, Temodar

Arm I (ACTIVATE); Arm II (ACT II STD); Arm III (ACT II DI)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed newly diagnosed glioblastoma multiforme
• Has undergone prior gross total resection (GTR) followed by conformal radiotherapy\* with or without concurrent chemotherapy
• GTR is defined as ≥ 95% volumetric resection of the contrast-enhancing component on the preoperative MRI
• Residual radiographic contrast enhancement on post-resection CT scan or MRI must be ≤ 1 cm in maximal diameter in any two perpendicular axial planes
• No evidence of disease progression after completion of radiotherapy\* NOTE: \*Patients may enroll in part 2 of the study within 2 weeks after surgery; these patients will receive radiotherapy with concurrent chemotherapy during the study
• EGFRvIII-positive tumor by immunohistochemistry, polymerase chain reaction, or related molecular techniques
• Karnofsky performance status 80-100%
• Curran group status I-IV
• Signed informed consent form

You may not qualify if:

• Absolute Neutrophil Count (ANC) \< 1,000/mm³
• Platelet count \< 50,000/mm³
• Prothrombin Time/Partial Thromboplastin Time (PT/PTT) \> 1.5 times normal
• Positive hepatitis B (HB) surface antigen (HbsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc)
• Pregnant or nursing
• Positive pregnancy test
• Active infection requiring treatment
• Unexplained febrile illness (T max \> 101.5 F)
• Inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or other autoimmune disease
• Known immunosuppressive disease
• Known HIV infection
• Diffuse leptomeningeal disease
• Unstable or severe concurrent medical condition, such as severe heart and lung disease or active hepatitis
• Demonstrated allergy to temozolomide or inability to tolerate temozolomide for reasons other than lymphopenia
• Concurrent corticosteroids (except for nasal or inhaled steroids) at a dose above physiologic levels (\> 2 mg of dexamethasone/day).

Sponsors & Collaborators

• John Sampson: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Related Publications (3)

• Schmittling RJ, Archer GE, Mitchell DA, Heimberger A, Pegram C, Herndon JE 2nd, Friedman HS, Bigner DD, Sampson JH. Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines. J Immunol Methods. 2008 Nov 30;339(1):74-81. doi: 10.1016/j.jim.2008.08.004. Epub 2008 Sep 4.

  PMID: 18775433 RESULT

• Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, Gilbert MR, Herndon JE 2nd, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling RJ, Shi W, Vredenburgh JJ, Bigner DD. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010 Nov 1;28(31):4722-9. doi: 10.1200/JCO.2010.28.6963. Epub 2010 Oct 4.

  PMID: 20921459 RESULT

• Sampson JH, Aldape KD, Archer GE, Coan A, Desjardins A, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling R, Shi W, Vredenburgh JJ, Bigner DD, Heimberger AB. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol. 2011 Mar;13(3):324-33. doi: 10.1093/neuonc/noq157. Epub 2010 Dec 10.

  PMID: 21149254 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

sargramostim; Temozolomide

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. John H. Sampson
• Organization: Duke University Medical Center

john.sampson@duke.edu

919-684-9041

Study Officials

• Gordana Vlahovic, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: March 25, 2008
• First Posted: March 26, 2008
• Study Start: September 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: November 1, 2016
• Last Updated: February 1, 2017
• Results First Posted: February 17, 2014

Record last verified: 2016-12

Locations

US (2)