Malignant Neoplasms of BrainPhase 1ZAP ITNCT00626015
Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery
A Phase 1 study testing PEP-3-KLH conjugate vaccine, daclizumab and temozolomide in people with Malignant Neoplasms of Brain, run by John Sampson at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Malignant Neoplasms of Brain
- What is being tested?
- PEP-3-KLH conjugate vaccine, daclizumab and temozolomide
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Feb 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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 locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: 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.
Read the 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.
- Conditions
- Malignant Neoplasms of Brain
- Being tested
- PEP-3-KLH conjugate vaccine, daclizumab, temozolomide, placebo, PEP-3-KLH
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult high grade glioma
- Medical subject headings
- Glioblastoma, Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEP-3-KLH conjugate vaccineBiological
Given intradermally
daclizumabBiological
Given IV
temozolomideDrug
Given by mouth.
placeboOther
Given IV
PEP-3-KLHBiological
Also called CDX-110, EGFRvIII-KLH
Basiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only.
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Temozolomide, PEP-3-KLH conjugate vaccine, and daclizumab Receives: Biological: PEP-3-KLH conjugate vaccine; Biological: daclizumab; Drug: temozolomide |
| Arm II | Experimental | Temozolomide, PEP-3-KLH conjugate vaccine, and normal saline Receives: Biological: PEP-3-KLH conjugate vaccine; Drug: temozolomide; Other: placebo |
| Basiliximab | Experimental | Patients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide. Receives: Biological: PEP-3-KLH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells
Measured: 26 months
Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab)
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2008 (estimated)
- Study startMar 2007
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Neoplasms of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Sampson
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, John Sampson, Duke University
- Investigators
- Duane Mitchell, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00626015
- Sponsor's protocol ID
- Pro00000947
- Other IDs
- R21CA132891, CDR0000579573
- Acronym
- ZAP IT
- Status last verified
- Jan 2016
- First submitted
- 28 Feb 2008
- Last updated
- 21 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Mitchell DA. A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One. 2012;7(2):e31046. doi: 10.1371/journal.pone.0031046. Epub 2012 Feb 27.
PubMed 22383993
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]
- ClinicalTrials.gov ID
- NCT00626015
- Acronym / sponsor ID
- ZAP IT / Pro00000947
- Conditions
- Malignant Neoplasms of Brain
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult high grade glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- John SampsonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2007
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 29 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: PEP-3-KLH conjugate vaccine, Biological: daclizumab, Drug: temozolomideTemozolomide, PEP-3-KLH conjugate vaccine, and daclizumab |
| Arm II | Experimental | Biological: PEP-3-KLH conjugate vaccine, Drug: temozolomide, Other: placeboTemozolomide, PEP-3-KLH conjugate vaccine, and normal saline |
| Basiliximab | Experimental | Biological: PEP-3-KLHPatients will receive basiliximab 20 mg IV with vaccine # 1 only and continue with PEP-3-KLH, temozolomide. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEP-3-KLH conjugate vaccineGiven intradermally | Biological | Arm I, Arm II |
| daclizumabGiven IV | Biological | Arm I |
| temozolomideGiven by mouth. | Drug | Arm I, Arm II |
| placeboGiven IV | Other | Arm II |
| PEP-3-KLHAlso: CDX-110, EGFRvIII-KLHBasiliximab 20 mg IV over 30 minutes with PEP-3-KLH vaccine # 1 only. | Biological | Basiliximab |
Primary outcome
Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells
Time frame: 26 months
Comparison of proliferative T-cell response to phytohemagglutinin (PHA) among treatment groups (with versus without daclizumab/basiliximab)
Time frame: 26 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2016.
- Results publication: PubMed 22383993Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Mitchell DA. A pilot study of IL-2Ralpha blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One. 2012;7(2):e31046. doi: 10.1371/journal.pone.0031046. Epub 2012 Feb 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Duane Mitchell, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PEP-3-KLH conjugate vaccine, daclizumab and temozolomide in people with Malignant Neoplasms of Brain, run by John Sampson at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells (time frame: 26 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00626015, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2016.