Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery

NCT00626015 | Completed Phase 1 DMC

• 3 other identifiers: Pro00000947R21CA132891CDR0000579573
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vaccines may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as basiliximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving chemotherapy, radiation therapy, and vaccine therapy together with basiliximab is a more effective treatment for glioblastoma multiforme than chemotherapy, radiation therapy, and vaccine therapy alone. PURPOSE: This randomized phase I trial is studying the side effects and best way to give chemotherapy and radiation therapy followed by vaccine therapy with basiliximab in treating patients with glioblastoma multiforme that has been removed by surgery.

Conditions

Malignant Neoplasms of Brain

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult high grade glioma

Outcome Measures

Primary Outcomes (2)

• Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells

  26 months

• Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab)

  26 months

Study Arms (3)

Arm I

EXPERIMENTAL

Temozolomide, PEP-3-KLH conjugate vaccine, and daclizumab

Biological: PEP-3-KLH conjugate vaccine; Biological: daclizumab; Drug: temozolomide

Arm II

EXPERIMENTAL

Temozolomide, PEP-3-KLH conjugate vaccine, and normal saline

Biological: PEP-3-KLH conjugate vaccine; Drug: temozolomide; Other: placebo

Basiliximab

EXPERIMENTAL

Patients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide.

Biological: PEP-3-KLH

Interventions

PEP-3-KLH conjugate vaccine BIOLOGICAL

Given intradermally

Arm I; Arm II

daclizumab BIOLOGICAL

Given IV

Arm I

temozolomide DRUG

Given by mouth.

Arm I; Arm II

placebo OTHER

Given IV

Arm II

PEP-3-KLH BIOLOGICAL

Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.

Also known as: CDX-110, EGFRvIII-KLH

Basiliximab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histopathologic diagnosis of WHO grade III or WHO grade IV high grade glioma * Newly diagnosed disease * Meets the following criteria: * The patient must undergo leukapheresis for immunologic monitoring * Tumor expression of EGFRvIII by immunohistochemistry (IHC) or polymerase chain reaction (PCR) * No radiographic or cytologic evidence of leptomeningeal or multicentric disease PATIENT CHARACTERISTICS: * Karnofsky performance status ≥ 80% * Curran Group status of I-IV * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No conditions that will potentially confound the study results, including any of the following: * Active infection requiring treatment or an unexplained febrile (\> 101.5°F) illness * Known immunosuppressive disease or known HIV infection * Unstable or severe intercurrent medical conditions such as severe heart or lung disease * No demonstrated allergy to TMZ * Able to tolerate TMZ * TMZ-induced lymphopenia allowed * No prior allergic reaction to daclizumab/basiliximab or its components PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No other conventional therapeutic intervention other than steroids, radiation, or temozolomide (TMZ) prior to enrollment * No prior allogeneic solid organ transplantation * No prior inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies * No corticosteroids at a dose above physiologic level except nasal or inhaled steroid at the time of first study vaccination * For the purposes of this study, physiologic dose is defined as \< 2 mg of dexamethasone/day * Once study vaccinations have been initiated, if patients subsequently require increased steroids, they are permitted to remain on the study * No prior daclizumab/basiliximab

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

Sponsors & Collaborators

• John Sampson: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Mitchell DA. A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One. 2012;7(2):e31046. doi: 10.1371/journal.pone.0031046. Epub 2012 Feb 27.

  PMID: 22383993 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma

Interventions

Daclizumab; Temozolomide; rindopepimut

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Duane Mitchell, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurosurgery

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: February 29, 2008
• Study Start: March 1, 2007
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: January 21, 2016

Record last verified: 2016-01

Locations

US (1)