cropped color_logo_with_background.png

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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00626015
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

John Sampson
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Duane Mitchell, MD, PhD
Principal Investigator Affiliation Duke University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Malignant Neoplasms of Brain
Additional Details

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.

Arms & Interventions

Arms

Experimental: Arm I

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

Experimental: Arm II

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

Experimental: Basiliximab

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

Interventions

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Duke University Medical Center, Durham, North Carolina

Status

Address

Duke University Medical Center

Durham, North Carolina, 27710