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Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (ACTIVATe)

2 grudnia 2016 zaktualizowane przez: John Sampson

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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

40

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Stany Zjednoczone
    • North Carolina
      • Durham, North Carolina, Stany Zjednoczone, 27710
        • Duke University Medical Center
    • Texas
      • Houston, Texas, Stany Zjednoczone, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • Histologically confirmed newly diagnosed glioblastoma multiforme

  • Has undergone prior gross total resection (GTR) followed by conformal radiotherapy* with or without concurrent chemotherapy

    • GTR is defined as ≥ 95% volumetric resection of the contrast-enhancing component on the preoperative MRI
    • Residual radiographic contrast enhancement on post-resection CT scan or MRI must be ≤ 1 cm in maximal diameter in any two perpendicular axial planes
    • No evidence of disease progression after completion of radiotherapy* NOTE: *Patients may enroll in part 2 of the study within 2 weeks after surgery; these patients will receive radiotherapy with concurrent chemotherapy during the study
  • EGFRvIII-positive tumor by immunohistochemistry, polymerase chain reaction, or related molecular techniques
  • Karnofsky performance status 80-100%
  • Curran group status I-IV
  • Signed informed consent form

Exclusion Criteria:

  • Absolute Neutrophil Count (ANC) < 1,000/mm³
  • Platelet count < 50,000/mm³
  • Prothrombin Time/Partial Thromboplastin Time (PT/PTT) > 1.5 times normal
  • Positive hepatitis B (HB) surface antigen (HbsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc)
  • Pregnant or nursing
  • Positive pregnancy test
  • Active infection requiring treatment
  • Unexplained febrile illness (T max > 101.5 F)
  • Inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or other autoimmune disease
  • Known immunosuppressive disease
  • Known HIV infection
  • Diffuse leptomeningeal disease
  • Unstable or severe concurrent medical condition, such as severe heart and lung disease or active hepatitis
  • Demonstrated allergy to temozolomide or inability to tolerate temozolomide for reasons other than lymphopenia
  • Concurrent corticosteroids (except for nasal or inhaled steroids) at a dose above physiologic levels (> 2 mg of dexamethasone/day).

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Arm I (ACTIVATE)
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), referred to as PEP-3 vaccine, every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.
Biologiczny: sargramostym
Podawany śródskórnie
Biologiczny: PEP-3 vaccine
Given intradermally
Lek: Temozolomide
Standard of care chemotherapy
Inne nazwy:
  • Temodara
  • TMZ
Eksperymentalny: Arm II (ACT II 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), referred to as PEP-3 vaccine, biweekly starting within 6 weeks of completing radiation. Additional vaccinations were 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.
Biologiczny: sargramostym
Podawany śródskórnie
Biologiczny: PEP-3 vaccine
Given intradermally
Lek: Temozolomide
Standard of care chemotherapy
Inne nazwy:
  • Temodara
  • TMZ
Eksperymentalny: Arm III (ACT II 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), referred to as PEP-3 vaccine, biweekly starting within 6 weeks of completing radiation. Additional vaccinations were 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.
Biologiczny: sargramostym
Podawany śródskórnie
Biologiczny: PEP-3 vaccine
Given intradermally
Lek: Temozolomide
Standard of care chemotherapy
Inne nazwy:
  • Temodara
  • TMZ

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Humoral and Cellular Immune Response
Ramy czasowe: 26 months
Number of patients that developed a delayed-type hypersensitivity (DTH) response at following vaccination. Any skin reaction in response to the intradermal injection of the antigen was measured and recorded. A positive skin test was defined as > 5 mm induration (swelling).
26 months
Clinical Efficacy of Vaccination, in Terms of Progression-free Survival (PFS)
Ramy czasowe: 58 months

Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).
58 months

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Response to Vaccination
Ramy czasowe: 26 months
The objective is to assess the duration of immunosuppressive cytokine secretion and to identify a receptive interval for active immunotherapy. Immunosuppression will determined by monitoring a panel of immunosuppressive serum/plasma cytokines longitudinally and by determining the response of each patient to Recombivax Hepatitis B (HB) vaccination. Response is defined as seropositive or seronegative to the Hepatitis B surface antigen.
26 months
Toxicity to PEP-3 Vaccine Immunization
Ramy czasowe: 26 months
To assess for any potential toxicity to the PEP-3 vaccine immunization in patients with newly diagnosed glioblastoma, Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to tabulate any toxicities attributable to PEP-3. The number of patients with toxicity attributable to vaccine while on study are tabulated.
26 months

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

John Sampson

Współpracownicy

National Institute of Neurological Disorders and Stroke (NINDS)

Śledczy

  • Główny śledczy: Gordana Vlahovic, MD, Duke University

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 września 2007

Zakończenie podstawowe (Rzeczywisty)

1 stycznia 2012

Ukończenie studiów (Rzeczywisty)

1 listopada 2016

Daty rejestracji na studia

Pierwszy przesłany

25 marca 2008

Pierwszy przesłany, który spełnia kryteria kontroli jakości

25 marca 2008

Pierwszy wysłany (Oszacować)

26 marca 2008

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

1 lutego 2017

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

2 grudnia 2016

Ostatnia weryfikacja

1 grudnia 2016

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • Pro00004040
  • P50NS020023 (Grant/umowa NIH USA)
  • CDR0000589632 (Inny identyfikator: National Cancer Institute)
  • DUMC-5421 (Identyfikator rejestru: DUMC IRB)

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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