Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery (ZAP IT)
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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.
| Condition | Intervention | Phase |
|---|---|---|
|
Malignant Neoplasms of Brain |
Biological: PEP-3-KLH conjugate vaccine Biological: daclizumab Drug: temozolomide Other: placebo Biological: PEP-3-KLH |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT] |
- Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells [ Time Frame: 26 months ] [ Designated as safety issue: No ]
- Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab) [ Time Frame: 26 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | March 2007 |
| Estimated Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| Principal Investigator: | Duane Mitchell, MD, PhD | Duke University |
More Information
Additional Information:
No publications provided by Duke University
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | John Sampson, Professor of Neurosurgery, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00626015 History of Changes |
| Other Study ID Numbers: | Pro00000947, R21CA132891, CDR0000579573 |
| Study First Received: | February 28, 2008 |
| Last Updated: | May 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Duke University:
|
adult glioblastoma adult giant cell glioblastoma adult gliosarcoma adult high grade glioma |
Additional relevant MeSH terms:
|
Brain Neoplasms Neoplasms Glioblastoma Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type |
Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Daclizumab Basiliximab Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 19, 2013