Clinical Trials /

Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma

NCT02546102

Description:

ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA) present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target glioblastoma tumour cells.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Suspended

Phase:

Phase 3

Trial Eligibility

Document

Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in <span class="go-doc-concept go-doc-disease">Glioblastoma</span>

Title

  • Brief Title: Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma
  • Official Title: A Phase 3 Randomized Double-blind, Controlled Study of ICT-107 With Maintenance Temozolomide (TMZ) in Newly Diagnosed Glioblastoma Following Resection and Concomitant TMZ Chemoradiotherapy
  • Clinical Trial IDs

    NCT ID: NCT02546102

    ORG ID: ICT-107-301

    Trial Conditions

    Glioblastoma Multiforme

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are
    pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA)
    present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients
    with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care
    chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with
    the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target
    glioblastoma tumour cells.

    Detailed Description

    This is a double blind Phase III study where eligible subjects are randomized into two
    treatment arms following the SOC primary treatment with chemoradiation: Arm 1 will receive
    ICT-107 in combination with the standard of care, temozolomide (TMZ), Arm 2 will receive TMZ
    with a blinded control. A 1:1 randomization will be employed, where ARM 1 will receive
    ICT-107 and Arm 2 will receive placebo control. All subjects must be HLA-A2+. All subjects
    must have glioblastoma tissue that has tumor assessment for MGMT methylation status prior to
    randomization (for stratification). Subjects will have had tumor resection and magnetic
    resonance imaging (MRI) prior to enrollment into the study. After signing of written
    informed consent and any required privacy compliance forms and screening, enrolled subjects
    will undergo large volume apheresis at the study site for collection of PBMCs. Apheresis
    product will be sent to the manufacturing site where both active therapy (ICT-107) and
    control will be prepared for each subject prior to randomization The study period consists
    of 4 time periods; a 6-week Post-Surgery Standard of Care Treatment Phase where subjects
    receive radiotherapy and TMZ; TMZ and radiation to be initiated no more than 8 weeks after
    surgical resection of glioblastoma; a Rest Period of no more than 14 days where subjects are
    reassessed for eligibility, and then randomized; a 4 week Induction Phase where study
    therapy (ICT-107 or Control) is given weekly; followed by a Maintenance Phase where study
    therapy is given monthly for 11 months, and then every 6 months until either progression,
    withdrawal from the study, death, or the supply of autologous study therapy is exhausted.
    Randomized subjects will receive 4 weekly administrations of subject-specific study therapy
    (ICT-107 or Control) during the Induction Phase. No TMZ will be given during the 4 week
    Induction Phase. Each study therapy injection will be delivered intradermally (axilla).

    The Maintenance Phase will consist of administration of subject-specific study therapy
    monthly for 11 months after the Induction Phase (for a total of 15 injections over 12 months
    during the Induction and Maintenance Phases), and then every 6 mos. thereafter until
    depletion or confirmation of progressive disease (PD). During the Maintenance Phase (where
    ICT-107 or control are given monthly), the administration of TMZ and subject specific study
    therapy or control will be separated in time by approximately 2 weeks (see Section 9.1.4).
    Pre-treatment, treatment and assessment schedules will be the same for all subjects.

    Trial Arms

    Name Type Description Interventions
    1 Experimental Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ). ICT-107 will be given once a week for 4 weeks in the induction phase. During the maintenance phase, ICT-107 will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.
    2 Placebo Comparator Arm 2 will receive TMZ with a blinded control. Control will be given once a week for 4 weeks in the induction phase. During the maintenance phase, Control will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.

    Eligibility Criteria

    Inclusion Criteria:

    1. Subjects must understand and sign the study specific informed consent

    2. Subjects must be in primary remission

    3. Subjects should have < 1 cm3 disease by MRI within the previous 4 weeks as defined by
    iRANO (by central read)

    4. Subjects must be HLA-A2 positive by central lab

    5. Subjects must have adequate renal, hepatic and bone marrow function based on
    screening laboratory assessments. Baseline hematologic studies and chemistry and
    coagulation profiles must meet the following criteria:

    1. Hemoglobin (Hgb) > 8 g/dL

    2. Absolute Neutrophil Count (ANC) > 1000/mm3

    3. Platelet count > 100,000/mm3

    4. Blood Urea Nitrogen (BUN) < 30 mg/dL

    5. Creatinine < 2 mg/dL

    6. Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine
    Aminotransferase (ALT) < 2 x upper limit of normal (ULN)

    7. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) 1.6x
    unless therapeutically warranted

    6. Subjects must use effective contraceptive methods during the study and for three
    months following the last dose of study product, if of reproductive age and still
    retain fertility potential.

    7. Subjects must have at least one positive DTH skin response (more than 5 mm) to test
    item challenge prior to randomization.

    Exclusion Criteria:

    1. Subjects receiving investigational study drug for any indication or
    immunological-based treatment for any reason (Filgrastim may be used for prevention
    of severe neutropenia).

    2. Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)

    3. Subjects with concurrent conditions that would jeopardize the safety of the subject
    or compliance with the protocol.

    4. Subjects with a history of chronic or acute hepatitis C or B infection.

    5. Subjects require or are likely to require more than a 2-week course of
    corticosteroids for intercurrent illness. Subjects must have completed the course of
    corticosteroids at the time of apheresis to meet eligibility.

    6. Subjects have any acute infection that requires specific therapy. Acute therapy must
    have been completed within seven days prior to study enrollment.

    7. Subjects with active malignancy diagnosed in the past 3 years (excepting in situ
    tumors)

    8. Subjects known to be pregnant or nursing.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall survival

    Secondary Outcome Measures

    Overall survival in patients with unmethylated MGMT tumors

    Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors

    Progression-free survival

    Type and frequency of treatment emergent adverse events

    Trial Keywords