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

January 20, 2016 updated by: John Sampson

Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Other: placebo
Given IV
Biological: PEP-3-KLH conjugate vaccine
Given intradermally
Drug: temozolomide
Given by mouth.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells
Time Frame: 26 months
26 months
Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab)
Time Frame: 26 months
26 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

John Sampson

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Duane Mitchell, MD, PhD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

February 28, 2008

First Submitted That Met QC Criteria

February 28, 2008

First Posted (Estimate)

February 29, 2008

Study Record Updates

Last Update Posted (Estimate)

January 21, 2016

Last Update Submitted That Met QC Criteria

January 20, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00000947
  • R21CA132891 (U.S. NIH Grant/Contract)
  • CDR0000579573 (Other Identifier: National Cancer Institute)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malignant Neoplasms of Brain

Clinical Trials on placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bangladesh

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe