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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00626015
Recruitment Status : Completed
First Posted : February 29, 2008
Last Update Posted : January 21, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
John Sampson, Duke University

Tracking Information
First Submitted Date  ICMJE February 28, 2008
First Posted Date  ICMJE February 29, 2008
Last Update Posted Date January 21, 2016
Study Start Date  ICMJE March 2007
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2010)
  • Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells [ Time Frame: 26 months ]
  • Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab) [ Time Frame: 26 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2008)
  • Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells
  • Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab)
Change History Complete list of historical versions of study NCT00626015 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery
Official Title  ICMJE Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Neoplasms of Brain
Intervention  ICMJE
  • Biological: PEP-3-KLH conjugate vaccine
    Given intradermally
  • Biological: daclizumab
    Given IV
  • Drug: temozolomide
    Given by mouth.
  • Other: placebo
    Given IV
  • Biological: PEP-3-KLH
    Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.
    Other Names:
    • CDX-110
    • EGFRvIII-KLH
Study Arms  ICMJE
  • Experimental: Arm I
    Temozolomide, PEP-3-KLH conjugate vaccine, and daclizumab
    Interventions:
    • Biological: PEP-3-KLH conjugate vaccine
    • Biological: daclizumab
    • Drug: temozolomide
  • Experimental: Arm II
    Temozolomide, PEP-3-KLH conjugate vaccine, and normal saline
    Interventions:
    • Biological: PEP-3-KLH conjugate vaccine
    • Drug: temozolomide
    • Other: placebo
  • Experimental: Basiliximab
    Patients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide.
    Intervention: Biological: PEP-3-KLH
Publications * 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-2Rα 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2014)
16
Original Enrollment  ICMJE
 (submitted: February 28, 2008)
20
Actual Study Completion Date  ICMJE February 2013
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00626015
Other Study ID Numbers  ICMJE Pro00000947
R21CA132891 ( U.S. NIH Grant/Contract )
CDR0000579573 ( Other Identifier: National Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party John Sampson, Duke University
Study Sponsor  ICMJE John Sampson
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Duane Mitchell, MD, PhD Duke University
PRS Account Duke University
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP