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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]

Conditions
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Malignant Neoplasms of Brain

Intervention / Treatment
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* Biological: PEP-3-KLH conjugate vaccine
* Biological: daclizumab
* Drug: temozolomide
* Other: placebo
* Biological: PEP-3-KLH


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Temozolomide, PEP-3-KLH conjugate vaccine, and daclizumab | Biological: PEP-3-KLH conjugate vaccine<br>* Given intradermally<br>Biological: daclizumab<br>* Given IV<br>Drug: temozolomide<br>* Given by mouth.<br>|
| Experimental: Arm II<br>Temozolomide, PEP-3-KLH conjugate vaccine, and normal saline | Biological: PEP-3-KLH conjugate vaccine<br>* Given intradermally<br>Drug: temozolomide<br>* Given by mouth.<br>Other: placebo<br>* Given IV<br>|
| Experimental: Basiliximab<br>Patients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide. | Biological: PEP-3-KLH<br>* Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.<br>* Other names: EGFRvIII-KLH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult high grade glioma