Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery
| Status: | Completed |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 4/21/2016 |
| Start Date: | March 2007 |
| End Date: | February 2013 |
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.
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.
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.
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.
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
We found this trial at
1
site
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
Click here to add this to my saved trials
