Malignant Neoplasms of Brain Clinical Trial
Official title:
A Complementary Trial of an Immunotherapy Vaccine Against Tumor-Specific EGFRvIII
RATIONALE: Vaccines made from a peptide may help the body build an effective immune response
to kill tumor cells. Colony-stimulating factors, such as GM-CSF, increase the number of
white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine
therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients
with newly diagnosed glioblastoma multiforme.
OBJECTIVES:
Primary
- To assess humoral and cellular immune responses to adjuvant PEP-3-KLH conjugate vaccine
in patients with newly diagnosed glioblastoma multiforme (GBM).
- To assess the clinical efficacy of the PEP-3-KLH conjugate vaccine, in terms of
progression-free survival, in patients with newly diagnosed GBM.
Secondary
- To determine whether patients with GBM, who are known to be at least mildly
immunosuppressed, can respond to standard and proven vaccine strategies.
- To assess for any potential toxicity to the PEP-3-KLH conjugate vaccine in patients
with newly diagnosed GBM.
OUTLINE: This is a multicenter study. Patients are stratified according to participating
center.
At the time the study was initiated, standard of care temozolomide was not established,
therefore, Arm I (ACTIVATE)was given without monthly cycles of temozolomide. At the point of
interim analysis, monthly cycles of temozolomide had become standard of care. Arm II was
then given the standard of care 5-day cycles of monthly temozolomide and during this time,
dose-intensified temozolomide was in trials to compare with the 5-day temozolomide.
Therefore, Arm III was initiated to determine the immunologic effects of 21-day monthly
cycles of temozolomide with vaccine.
- Arm I (ACTIVATE): Patients receive PEP-3-KLH conjugate vaccine and sargramostim
(GM-CSF) intradermally on days 1, 15, and 29 and then monthly in the absence of disease
progression or unacceptable toxicity.
- Arm II (ACT II Standard (STD)): Patients first receive 3 initial vaccinations of an
epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3)
keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly
starting within 6 weeks of completing radiation. Additional vaccinations are given
until clinical or radiographic evidence of progression or death. Patients subsequently
receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day
cycle.
- Arm III (ACT II Dose-intensified (DI)): Patients first receive 3 initial vaccinations
of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3)
keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly
starting within 6 weeks of completing radiation. Additional vaccinations are given
until clinical or radiographic evidence of progression or death. Patients subsequently
receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day
cycle.
- Patients undergo delayed-type hypersensitivity (DTH) skin testing* at baseline,
after the third vaccination, and then monthly thereafter. Patients also undergo
leukapheresis to obtain sufficient peripheral blood lymphocytes for immunologic
monitoring at baseline, after the third vaccination, and then, if applicable, at
the time of positive DTH response, disease progression, or after the sixth course
of post-radiotherapy temozolomide. Methods used for immunologic monitoring include
Enzyme-linked Immunospot(ELISPOT) assays, cytotoxicity assays, fluorescence
activated cell sorting (FACS), and ELISA.
NOTE: *Patients with positive DTH skin testing, also undergo skin punch biopsies.
After completion of study therapy, patients are followed periodically.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00626015 -
Chemotherapy, Radiation Therapy, and Vaccine Therapy With Basiliximab in Treating Patients With Glioblastoma Multiforme That Has Been Removed by Surgery
|
Phase 1 | |
| Completed |
NCT00639639 -
Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
|
Phase 1 |