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

Sponsor

John Sampson (Other)

Overall Status

Completed

CT.gov ID

NCT00626015

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

71.1

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

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	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

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

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

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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