Clinical Trials /

Phase I EGFR BATs in Newly Diagnosed Glioblastoma

NCT03344250

Description:

This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy and will require a minimum of 3 and a maximum of 18 patients to identify this dose.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I EGFR BATs in Newly Diagnosed Glioblastoma
  • Official Title: A Phase I Study Targeting Newly Diagnosed Glioblastoma With Anti-CD3 × Anti-EGFR Bispecific Antibody Armed T Cells (EGFR BATs) in Combination With Radiation and Temozolomide

Clinical Trial IDs

  • ORG STUDY ID: 20105
  • NCT ID: NCT03344250

Conditions

  • Glioblastoma
  • Glioblastoma Multiforme

Interventions

DrugSynonymsArms
EGFR BATs with SOC RT and TMZEGFR BATs with SOC RT and TMZ

Purpose

This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy and will require a minimum of 3 and a maximum of 18 patients to identify this dose.

Detailed Description

      In addition to finding the safe dose of EGFR BATs, immune evaluations will be performed as
      delineated in the schedule of events to measure immune responses during all stages of
      treatment for GBM.
    

Trial Arms

NameTypeDescriptionInterventions
EGFR BATs with SOC RT and TMZExperimentalStudy participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. Participants will receive the first and second infusions of EGFR BATs on days 14 and 21 after finishing concurrent RT and TMZ and then receive an infusion on day 21 of the first six cycles of TMZ.
  • EGFR BATs with SOC RT and TMZ

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically-confirmed newly diagnosed intracranial GBM or gliosarcoma

          2. Age ≥ 18 years.

          3. Karnofsky Performance Status ≥ 60.

          4. Be willing and able to provide written informed consent for the trial.

          5. For patients with resection, CT/MRI with contrast must be performed within 72 hours
             following resection. Intraoperative post resection MRI is acceptable. No post surgery
             CT/MRI is required for patients who have received biopsy.

          6. Females of childbearing potential, and males, must be willing to use an effective
             method of contraception

          7. Females of childbearing potential should have a negative urine or serum pregnancy
             test. If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required.

          8. Demonstrate adequate organ function as defined below. All screening labs should be
             performed within 10 days prior to apheresis.

        Absolute lymphocyte count ≥ 500/mm3, Absolute neutrophil count (ANC) ≥1,000 /mcL, Platelets
        ≥ 100,000 / mcL, Hemoglobin ≥ 9 g/dL (or ≥5.6 mmol/L without transfusion or EPO dependency
        (within 7 days of assessment), BUN ≤ 1.5 X upper limit of normal (ULN), Serum creatinine
        within the normal limits OR Measured or calculated creatinine clearance ≥60 mL/min/1.73m2,
        Serum total bilirubin ≤ 1.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 X ULN, Albumin >2.5
        mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN, unless
        subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
        of intended use of anticoagulants

        Exclusion Criteria:

          1. Patients with a diagnosis of another malignancy within 3 years of being on-study.
             Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.
             Patients must not be on any treatment for another malignancy.

          2. Patients with evidence of leptomeningeal dissemination or subependymal spread on
             initial MRI.

          3. Patients with extracranial metastases.

          4. Known hypersensitivity to cetuximab or other EGFR antibody.

          5. Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range
             (indicating likely hypersensitivity to cetuximab)

          6. Evidence of active bleeding or bleeding diathesis.

          7. Cardiac Status: Patients will be ineligible for treatment on this protocol if (prior
             to protocol entry):

             There is a history of a recent (within one year) myocardial infarction or stroke.

             There is a current or prior history of angina/coronary symptoms requiring medications
             and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO).

             There is clinical evidence of congestive heart failure requiring medical management
             (irrespective of MUGA or ECHO results).

          8. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis
             B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

          9. Has received a live vaccine within 30 days of planned start of study therapy.

         10. Has received any treatment for GBM besides surgery.

         11. Females must not be breastfeeding.

         12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         13. A patient may be excluded if, in the opinion of the treating clinician, the patient is
             not capable of being compliant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:The study will not advance to the next dose until 7 days after the last patient in the cohort completes his or her second infusion of EGFR BATs
Safety Issue:
Description:Maximum tolerated dose will be based on number of dose limiting toxicities at each dose level

Secondary Outcome Measures

Measure:Immune measures in blood- cellular phenotype
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of cellular phenotype
Measure:Immune measures in blood- interferon-γ
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of interferon-γ
Measure:Immune measures in blood- EliSpots
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of EliSpots
Measure:Immune measures in blood- anti-GBM cytotoxicity of peripheral blood mononuclear cells directed at GBM cell lines
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of anti-GBM cytotoxicity of peripheral blood mononuclear cells directed at GBM cell lines
Measure:Immune measures in blood- serum cytokine patterns
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of serum cytokine patterns
Measure:Immune measures in blood- anti-GBM antibodies
Time Frame:Before surgery (when possible), during screening, at leukapheresis, at 1st and second infusion (2 and 3 weeks after completing RT), and on day 1 of cycles 1, 3, and 5, and 1, 3, 6, and 12 months after completion of EGFR BATs infusions
Safety Issue:
Description:Sequential monitoring of anti-GBM antibodies
Measure:Clinical response
Time Frame:Every 3 months following last study visit until death or study closure, expected within 5 years
Safety Issue:
Description:Progression-free survival (PFS)
Measure:Survival
Time Frame:Every 3 months following last study visit until death or study closure, expected within 5 years
Safety Issue:
Description:Overall Survival (OS)
Measure:Response Rate
Time Frame:Every 3 months following last study visit until death or study closure, expected within 5 years
Safety Issue:
Description:Objective Response Rate
Measure:Correlation of imaging to PFS and OS
Time Frame:Up to 12 months after study treatment completion
Safety Issue:
Description:Imaging (extent of resection) will be evaluated for correlation with PFS and OS.
Measure:Correlation of pathology to PFS and OS
Time Frame:Up to 12 months after study treatment completion
Safety Issue:
Description:EGFR expression and tumor-infiltrating lymphocytes and age will be evaluated for correlation with PFS and OS.
Measure:Correlation of clinical response to PFS and OS
Time Frame:Up to 12 months after study treatment completion
Safety Issue:
Description:Steroid use at the time of leukapheresis and age will be evaluated for correlation with PFS and OS.
Measure:Correlation of immune response to PFS and OS
Time Frame:Up to 12 months after study treatment completion
Safety Issue:
Description:Immune response characteristics will be evaluated for correlation with PFS and OS.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Virginia

Trial Keywords

  • Adoptive Cell Therapy
  • Armed Activated T-cells
  • Bispecific Antibodies
  • Immunotherapy

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