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

NCT02521090 | Withdrawn Phase 1 DMC

• 3 other identifiers: 2014-112NCI-2015-00232P30CA022453
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Adult Brain Glioblastoma; Adult Gliosarcoma; Recurrent Brain Neoplasm

Outcome Measures

Primary Outcomes (2)

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

  Up to 7 days after the last infusion

• 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.

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

Secondary Outcomes (6)

• Change in cytokines profiles

  Baseline to up to 1 year

• Changes in activated T cells

  Baseline to up to 1 year

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

  Baseline to up to 1 year

• Changes induced by IMT

  Baseline to up to 1 year

• Human anti-mouse antibody responses

  Up to 1 year

Other Outcomes (1)

• Persistence of aATC in blood

  Up to 1 year

Study Arms (1)

Treatment (EGFRBi-armed autologous T cells)

EXPERIMENTAL

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 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.

Biological: EGFRBi-Armed Autologous T Cells; Other: Laboratory Biomarker Analysis

Interventions

EGFRBi-Armed Autologous T Cells BIOLOGICAL

Given IT and IV

Treatment (EGFRBi-armed autologous T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (EGFRBi-armed autologous T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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):
• 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)

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Gliosarcoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Sandeep Mittal

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2015
• First Posted: August 13, 2015
• Study Start: August 1, 2015
• Primary Completion: March 1, 2016
• Last Updated: February 15, 2016

Record last verified: 2016-02