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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02546102
Recruitment Status : Suspended (Company at this time unable to secure sufficient financial resources to complete)
First Posted : September 10, 2015
Last Update Posted : August 13, 2018
Sponsor:
Collaborator:
Novella Clinical
Information provided by (Responsible Party):
Precision Life Sciences Group

Tracking Information
First Submitted Date  ICMJE September 7, 2015
First Posted Date  ICMJE September 10, 2015
Last Update Posted Date August 13, 2018
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
Overall survival [ Time Frame: 46 months ]
Overall survival (OS) of subjects treated with ICT-107 and standard of care (radiation (RT) and TMZ) vs. placebo control and standard of care (RT and TMZ)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02546102 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
  • Overall survival in patients with unmethylated MGMT tumors [ Time Frame: 46 months ]
    OS of subjects with unmethylated MGMT (O6-methylguanine-DNA methyltransferase) tumors treated with ICT-107 and standard of care vs. control and standard of care
  • Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors [ Time Frame: 46 months ]
    OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.
  • Progression-free survival [ Time Frame: 46 months ]
    Progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care
  • Type and frequency of treatment emergent adverse events [ Time Frame: 46 months ]
    Compare the type and frequency of treatment emergent adverse events of ICT-107 vs. control treatment groups
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE
  • Biological: ICT-107
    Autologous dendritic cells pulsed with peptides associated with tumor antigens
  • Biological: Placebo
Study Arms  ICMJE
  • Experimental: 1
    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.
    Intervention: Biological: ICT-107
  • Placebo Comparator: 2
    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.
    Intervention: Biological: Placebo
Publications * Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuño MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013 Jan;62(1):125-35. doi: 10.1007/s00262-012-1319-0. Epub 2012 Jul 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: September 9, 2015)
414
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (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 other malignancy diagnosed in the past 3 years (excepting in situ tumors)
  8. Subjects known to be pregnant or nursing.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02546102
Other Study ID Numbers  ICMJE ICT-107-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Precision Life Sciences Group
Study Sponsor  ICMJE Precision Life Sciences Group
Collaborators  ICMJE Novella Clinical
Investigators  ICMJE Not Provided
PRS Account Precision Life Sciences Group
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP