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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John Sampson, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00626015
First received: February 28, 2008
Last updated: July 29, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Malignant Neoplasms of Brain
Biological: PEP-3-KLH conjugate vaccine
Biological: daclizumab
Drug: temozolomide
Other: placebo
Biological: PEP-3-KLH
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells [ Time Frame: 26 months ] [ Designated as safety issue: No ]
  • Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab) [ Time Frame: 26 months ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2007
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Temozolomide, PEP-3-KLH conjugate vaccine, and daclizumab
Biological: PEP-3-KLH conjugate vaccine
Given intradermally
Biological: daclizumab
Given IV
Drug: temozolomide
Given by mouth.
Experimental: Arm II
Temozolomide, PEP-3-KLH conjugate vaccine, and normal saline
Biological: PEP-3-KLH conjugate vaccine
Given intradermally
Drug: temozolomide
Given by mouth.
Other: placebo
Given IV
Experimental: Basiliximab
Patients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide.
Biological: PEP-3-KLH
Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.
Other Names:
  • CDX-110
  • EGFRvIII-KLH

Detailed Description:

OBJECTIVES:

Primary

  • To determine if basiliximab inhibits the functional and numeric recovery of T-regulatory cells (Tregs) after therapeutic temozolomide (TMZ)-induced lymphopenia in the context of vaccinating adult patients with newly diagnosed glioblastoma multiforme (GBM) using PEPvIII-keyhole limpet hemocyanin (KLH).

Secondary

  • To evaluate the safety of basiliximab in the context of vaccinating adult patients with newly diagnosed GBM using PEP-3-KLH conjugate vaccine during recovery from therapeutic TMZ-induced lymphopenia.
  • To determine if basiliximab enhances the magnitude or character of PEPvIII-KLH-induced cellular or humoral immune responses, inhibits or enhances activation-induced cell death, or induces immunologic or clinical evidence of autoimmunity.
  • To determine if basiliximab enhances the magnitude or character of PEPvIII-KLH-induced cellular or humoral immune responses, inhibits or enhances activation-induced cell death, or induces immunologic or clinical evidence of autoimmunity.
  • To determine if basiliximab alters the phenotype (CD56-expression), cytokine secretion profile, or cytotoxicity of CD3-negative CD56-positive natural killer cells.
  • To determine if basiliximab, in addition to vaccination, extend progression-free survival compared to historical cohorts.
  • To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of antigen escape outgrowth.

OUTLINE:

  • Leukapheresis: Patients undergo leukapheresis over 2-4 hours for immunologic monitoring.
  • Concurrent standard adjuvant chemoradiotherapy: Patients receive external-beam radiotherapy once daily, 5 days a week, over 6-7 weeks (33 fractions) and concurrent temozolomide by mouth 7 days a week for up to 49 days beginning on the first day and continuing until the last day of radiotherapy.
  • Temozolomide and PEP-3-KLH conjugate vaccine: Approximately 3 weeks after completion of radiotherapy, patients receive temozolomide by mouth on days 1-21, or on days 1-5 depending on their treating neuro-oncologist, basiliximab IV over 30 minutes on day 21, and PEP-3-KLH conjugate vaccine intradermally on days 21, 35, and 49.

Patients then receive a second course of temozolomide by mouth on days 1-21 or days 1-5, depending on their treating neuro-oncologist. Treatment with temozolomide repeats every 4 weeks for 5 additional courses. Patients also receive PEP-3-KLH conjugate vaccine on day 21 of each remaining temozolomide course. Patients then receive the vaccine monthly until disease progression.

Patients undergo blood sample collection periodically for laboratory studies.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00626015

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
John Sampson
Investigators
Principal Investigator: Duane Mitchell, MD, PhD Duke University
  More Information

Additional Information:
Publications:
Responsible Party: John Sampson, Professor of Neurosurgery, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00626015     History of Changes
Other Study ID Numbers: Pro00000947, R21CA132891, CDR0000579573
Study First Received: February 28, 2008
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
adult high grade glioma

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Neoplasms
Astrocytoma
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Glioma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Nervous System Neoplasms
Neuroectodermal Tumors
Basiliximab
Daclizumab
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014