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Adult Brain GlioblastomaPhase 1/2NCT02521090

EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

A Phase 1/2 study testing EGFRBi-Armed Autologous T Cells and Laboratory Biomarker Analysis in people with Adult Brain Glioblastoma and Adult Gliosarcoma, run by Barbara Ann Karmanos Cancer Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EGFRBi-Armed Autologous T Cells and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2015to Mar 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically-confirmed intracranial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) with evidence of clinical and radiographic (computed tomography [CT] or MRI brain) tumor progression (need not be biopsy proven)
  • Patients who have undergone prior resection, radiation therapy, and/or chemotherapy (except bevacizumab)
  • Karnofsky performance score >= 70 or Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1
  • Patient agrees to undergo a baseline and a follow-up 11C-alpha-methyl-L-tryptophan (AMT)-PET scan during immunotherapy (IMT)
  • No serious medical or psychiatric illness which prevents informed consent or intensive treatment is allowed
  • Non pregnant: negative serum test for pregnancy, unless male, prior hysterectomy, tubal ligation, or postmenopausal; (Note: postmenopausal is defined as age > 55 with amenorrhea for > 1 year or age < 55 years with amenorrhea for 2 years and follicle stimulating hormone (FSH) level within postmenopausal range of institutional parameters; patients requiring FSH level to determine menopausal status need not have this performed and may choose to proceed with serum pregnancy testing)
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  • Required initial laboratory data (normal limits per treating institution; minor changes from the indicated laboratory guidelines will be allowed at the discretion of the treating team under special circumstances and reasons for the changes will be documented):
  • Granulocytes >= 1,000/mm^3
  • Absolute lymphocyte count >= 500/mm^3
  • Platelet count >= 50,000/ul
  • Hemoglobin >= 8 gm/dl
  • Blood urea nitrogen (BUN) =< 1.5 times normal
  • Serum creatinine < 1.8 mg/dl
  • Creatinine clearance >= 50 ml/mm (can be calculated utilizing the Cockcroft \& Gault equation)
  • Bilirubin < 1.5 times upper limit of normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal
  • Alkaline phosphatase < 5 times upper limit of normal
  • Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.2 times upper limit of normal
  • Negative human immunodeficiency virus (HIV)-1/2 serology
  • Negative hepatitis B surface antigen
  • Negative hepatitis C serology
  • Left ventricular ejection fraction (LVEF) >= 45% at rest (multi gated acquisition [MUGA] or echocardiogram [ECHO])
  • Each patient must be aware of the nature of their disease and must willingly consent to treatment after being informed of alternatives, potential benefits, side effects, and risks
  • Surgery is done prior to IMT if needed for palliation, tumor debulking, pathological documentation of tumor recurrence; the patients may continue on study therapy even if they do not have measurable disease
  • No other investigational agents, immunomodulating agents, or cancer chemotherapy are permitted for the duration and 12 months following the study IMT unless there is disease progression; radiotherapy is not permitted; appropriate antibiotics, blood products, antiemetics, fluids, electrolytes and general supportive care are to be used as necessary

Who cannot join

  • Resective surgery within 2 months prior to the initial pre-treatment AMT-PET scan
  • Severe increased intracranial pressure, status epilepticus, or other serious complications from the brain tumor, requiring emergency or urgent intervention
  • Patients with a history of another malignancy within 5 years of study enrollment
  • Patients with extracranial metastases
  • Evidence of active bleeding or bleeding diathesis
  • Patients will be ineligible for treatment on this protocol if (prior to protocol entry):
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  • There is a history of a recent (within one year) myocardial infarction
  • 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)

About this study

Official title: Targeting Recurrent Glioblastoma With Anti-CD3 x Anti-EGFR Bispecific Antibody Armed T Cells: A Phase I/II Study

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. EGFRBi-armed autologous T cells coated with antibodies (proteins used by the immune system to target and kill foreign objects such as cancer cells) may have great ability to seek out, attach to, and destroy glioblastoma cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) for 8 intrathecal (IT) injections (via lumbar puncture) of anti-cluster of differentiation (CD)3 × anti-EGFRBi armed activated T cells (aATC) (EGFRBi-armed autologous T cells) given twice per week for 4 weeks in a standard 3+3 dose escalation schema with 0.10, 0.50 and 1.00 × 10^9 EGFRBi-aATC per IT injection for a total of 0.8, 4.0, and 8.0 × 10^9 cells, respectively. (Phase I) II. To explore efficacy and confirm the toxicity profile of EGFRBi-aATC. (Phase II)

SECONDARY OBJECTIVES:

  1. Measure immune responses in participants of the phase I/II trial by sequential monitoring of phenotype, interferon gamma (IFN-g) enzyme-linked immunoSpots (EliSpots), anti-glioblastoma (GBM) cytotoxicity of peripheral blood mononuclear cell (PBMC) (direct cytotoxicity against GBM cells) directed at GBM cell lines, T-helper 1 (Th1)/T-helper 2 (Th2) serum cytokine patterns, and anti-glioma antibodies in the cerebrospinal fluid (CSF)/serum during the "vaccinate and consolidate" process.

II. Assess survival and persistence of aATC in the CSF, and trafficking of IT-injected aATC out of the CSF into the bloodstream.

III. Image patients' brain with magnetic resonance imaging (MRI) (performed clinically in 2-month intervals; includes standard structural sequences and perfusion imaging) and alpha-[11C]methyl-L-tryptophan (AMT) positron emission tomography (PET) scan (under Wayne State University [WSU] Internal Review Board [IRB]/Karmanos Cancer Institute [KCI]-approved research protocol) before and after the aATC treatment regimen.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

PHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks.

PHASE II: Patients receive EGFRBi-armed autologous T cells* IT twice weekly for 4 weeks and then intravenously (IV) over 15-30 minutes twice weekly for 2 weeks.

*NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1 prior to first IT infusion.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Being tested
EGFRBi-Armed Autologous T Cells, Laboratory Biomarker Analysis
Medical subject headings
Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EGFRBi-Armed Autologous T CellsBiological

    Given IT and IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02521090
Study groupRoleWhat they receive
Treatment (EGFRBi-armed autologous T cells)ExperimentalPHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks. PHASE II: Patients receive EGFRBi-armed autologous T cells* IT twice weekly for 4 weeks and then IV over 15-30 minutes twice weekly for 2 weeks. *NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1 prior to first IT infusion.
Receives: Biological: EGFRBi-Armed Autologous T Cells; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)

    Measured: Up to 7 days after the last infusion

  2. Overall survival (OS) (Phase II)

    The median OS will be estimated with 95% confidence interval. Kaplan-Meier estimate of OS will be plotted. For quantitative measurements in immune evaluations, will calculate their means, standard deviations, medians, and examine the distributions of these data to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT.

    Measured: From study enrollment to death due to any cause, assessed up to 2 years

Secondary outcomes (6)

  1. Change in cytokines profiles

    Mean, standard deviation, median and examine the distributions of these data will be calculated to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT. Bonferroni's adjusted p-values will be reported to control type I error rate. In addition, will assess the pattern of changes in the immune responses over time using graphical techniques such as LOWESS curves.

    Measured: Baseline to up to 1 year

  2. Changes in activated T cells

    Mean, standard deviation, median and examine the distributions of these data will be calculated to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT. Bonferroni's adjusted p-values will be reported to control type I error rate. In addition, will assess the pattern of changes in the immune responses over time using graphical techniques such as LOWESS curves.

    Measured: Baseline to up to 1 year

  3. Changes in cytotoxic T-lymphocyte as measured by IFN-gamma EliSpots directed at autologous tumor or GBM cell lines

    Mean, standard deviation, median and examine the distributions of these data will be calculated to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT. Bonferroni's adjusted p-values will be reported to control type I error rate. In addition, will assess the pattern of changes in the immune responses over time using graphical techniques such as LOWESS curves.

    Measured: Baseline to up to 1 year

  4. Changes induced by IMT

    Mean, standard deviation, median and examine the distributions of these data will be calculated to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT. Bonferroni's adjusted p-values will be reported to control type I error rate. In addition, will assess the pattern of changes in the immune responses over time using graphical techniques such as LOWESS curves.

    Measured: Baseline to up to 1 year

  5. Human anti-mouse antibody responses

    Serial serum samples will be tested and evaluated for the development of immunoglobulin G (IgG) and IgM anti-mouse antibody responses.

    Measured: Up to 1 year

  6. Peripheral blood measures

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2015 (estimated)
  2. Study startAug 2015
  3. Primary completionMar 2016 (estimated)

Why it stopped: Due to lack of funding and a primary co-investigator of the trial leaving the institution.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02521090
Sponsor's protocol ID
2014-112
Other IDs
NCI-2015-00232, 2014-112, P30CA022453
Status last verified
Feb 2016
First submitted
10 Aug 2015
Last updated
15 Feb 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EGFRBi-Armed Autologous T Cells and Laboratory Biomarker Analysis in people with Adult Brain Glioblastoma and Adult Gliosarcoma, run by Barbara Ann Karmanos Cancer Institute.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) (time frame: Up to 7 days after the last infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02521090.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2016.

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