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Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Malignant Neoplasms of Brain

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Trial Information

Zenapax®-Activated Peptide ImmunoTherapy [ZAP IT]


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Functional suppressive capacity of CD4+CD25+CD127- T-regulatory cells

Outcome Time Frame:

26 months

Safety Issue:

No

Principal Investigator

Duane Mitchell, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University

Authority:

United States: Food and Drug Administration

Study ID:

Pro00000947

NCT ID:

NCT00626015

Start Date:

March 2007

Completion Date:

November 2013

Related Keywords:

  • Malignant Neoplasms of Brain
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • adult high grade glioma
  • Brain Neoplasms
  • Neoplasms
  • Glioblastoma

Name

Location

Duke University Medical CenterDurham, North Carolina  27710