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Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma

This study is currently recruiting participants.
Verified September 2017 by City of Hope Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02208362
First Posted: August 5, 2014
Last Update Posted: September 4, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Gateway for Cancer Research
Mustang Bio, Inc.
Information provided by (Responsible Party):
City of Hope Medical Center
  Purpose

This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. T cells are taken from the patient's blood and a modified gene is placed into them in the laboratory and this may help them recognize and kill glioma cells. Genetically modified T-cells may also help the body build an immune response against the tumor cells.

Funding Source - FDA OOPD


Condition Intervention Phase
Malignant Glioma Refractory Brain Neoplasm Recurrent Brain Neoplasm Glioblastoma Biological: IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing Autologous T lymphocytes Other: laboratory biomarker analysis Other: quality-of-life assessment Procedure: Magnetic Resonance Imaging Procedure: Magnetic Resonance Spectroscopic Imaging Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Cellular Immunotherapy Using Central Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Specific, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Patients With Recurrent/Refractory Malignant Glioma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Incidence of grade 3 toxicity, graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0, the revised cytokine release syndrome grading system as well as the modified neurological grading system [ Time Frame: Up to 15 years ]
  • Incidence of DLT, graded using NCI CTCAE version 4.0 [ Time Frame: Up to 1 week following the last course (not including optional courses 4-6) ]
    Rate and associated 90% Clopper and Pearson binomial confidence limits (90% confidence interval) will be estimated for participants' experiencing DLTs at the RP2D schedule.

  • Incidence of toxicities, graded using NCI CTCAE version 4.0 as well as the modified neurological grading system [ Time Frame: Up to 15 years ]
    Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity and strata.


Secondary Outcome Measures:
  • Changes in largest length of tumor [ Time Frame: Baseline to up to 15 years ]
    Descriptive statistics will be provided for brain inflammation (largest length of tumor) pre and post treatment.

  • Changes in cytokine levels [ Time Frame: Baseline to up to 6 weeks ]
    Statistical and graphical methods will be used to describe the cytokine levels (cyst fluid, peripheral blood) over the study period.

  • Changes in CAR T cell levels [ Time Frame: Baseline to up to 6 weeks ]
    Statistical and graphical methods will be used to describe the CAR T cell levels (cyst fluid, peripheral blood) over the study period.

  • Progression free survival [ Time Frame: At 6 months ]
    Estimated using 90% confidence interval.

  • Disease response by the Response Assessment in Neuro-Oncology criteria [ Time Frame: Up to 15 years ]
    Estimated using 90% confidence interval.

  • Overall survival (OS) [ Time Frame: Up to 15 years ]
    Kaplan Meier methods will be used to estimate median overall survival and graph the results. OS will also be examined for all patients, as well as, separately for those that received initial treatment only and those that received intraventricular infusion following progression

  • Changes in quality of life [ Time Frame: Baseline to up to 15 years ]
    Estimate the mean and standard error for change from baseline during treatment and post treatment in the quality of life functioning scale, symptom scale and item scores from the EORTC QLQ-C30 and the domain scale and items scores from the QLQ-BN20.

  • T cell detection in tumor [ Time Frame: Up to 1 year ]
    In study participants that undergo a second resection or following autopsy, T cells numbers, location, and antigen levels will be described.

  • IL13Ra2 antigen expression levels [ Time Frame: Up to 1 year ]
  • Disease response from intraventricular infusion following progression after intracranial infusion (stratum 1 and 2) [ Time Frame: Up to 15 years ]
    Estimated using 90% confidence


Estimated Enrollment: 100
Actual Study Start Date: May 18, 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum I (T lymphocytes intratumoral)
Patients receive IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing T lymphocytes via intratumoral catheter over 5-10 minutes weekly for 3 weeks in the absence of disease progression. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Patients who progress on intracavitary or intratumoral administration may move to intraventricular catheter for the optional infusions.
Biological: IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing Autologous T lymphocytes
Given via intratumoral or intracavitary or intraventricular catheter
Other Name: autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T cells
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Procedure: Magnetic Resonance Imaging
Correlative studies
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance/Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
Procedure: Magnetic Resonance Spectroscopic Imaging
Correlative studies
Other Names:
  • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging
Experimental: Stratum II (T lymphocytes intracavitary)
Patients receive IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing T lymphocytes via intracavitary catheter over 5-10 minutes weekly for 3 weeks in the absence of disease progression. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Patients who progress on intracavitary or intratumoral administration may move to intraventricular catheter for the optional infusions.
Biological: IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing Autologous T lymphocytes
Given via intratumoral or intracavitary or intraventricular catheter
Other Name: autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T cells
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Procedure: Magnetic Resonance Imaging
Correlative studies
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance/Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
Procedure: Magnetic Resonance Spectroscopic Imaging
Correlative studies
Other Names:
  • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging
Experimental: Stratum III (T lymphocytes intraventricular)
Patients receive IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing T lymphocytes via intraventricular catheter over 5-10 minutes weekly for 3 weeks in the absence of disease progression. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Patients who progress on intracavitary or intratumoral administration may move to intraventricular catheter for the optional infusions.
Biological: IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing Autologous T lymphocytes
Given via intratumoral or intracavitary or intraventricular catheter
Other Name: autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T cells
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Procedure: Magnetic Resonance Imaging
Correlative studies
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance/Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
Procedure: Magnetic Resonance Spectroscopic Imaging
Correlative studies
Other Names:
  • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging
Experimental: Stratum IV (T lymphocytes intratumoral and intraventricular)
Patients receive IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing T lymphocytes via intratumoral catheter and intraventricular catheter over 5 minutes weekly for 3 weeks in the absence of disease progression. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites).
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Procedure: Magnetic Resonance Imaging
Correlative studies
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance/Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
Procedure: Magnetic Resonance Spectroscopic Imaging
Correlative studies
Other Names:
  • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging
Biological: IL13Rα2-specific, hinge-optimized, 41BB-costimulatory CAR/truncated CD19-expressing Autologous T lymphocytes
Given via intratumoral and intraventricular catheter
Other Name: autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T cells

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG) after completing standard therapy
  • Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial radiation therapy
  • Karnofsky performance status (KPS) >= 60%
  • Life expectancy > 4 weeks
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • COH Clinical Pathology confirms IL13R alpha 2+ tumor expression by immunohistochemistry (>= 20%, 1+)
  • All research participants must have the ability to understand and the willingness to sign a written informed consent

ELIGIBILITY TO PROCEED WITH PBMC COLLECTION:

  • Research participant must not require more than 2 mg TID of Dexamethasone on the day of PBMC collection
  • Research participant must have appropriate venous access
  • At least 2 weeks must have elapsed since the research participant received his/her last dose of prior chemotherapy or radiation

ELIGIBILITY TO PROCEED WITH RICKHAM PLACEMENT:

  • Creatinine < 1.6 mg/dL
  • White blood cell (WBC) > 2,000/dl
  • Absolute neutrophil count (ANC) > 1,000
  • Platelets >= 100,000/dl
  • International normalized ratio (INR) < 1.3
  • Bilirubin < 1.5 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x upper limits of normal
  • An interval of at least 12 weeks must have elapsed since the completion of initial radiation therapy
  • At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen
  • At least 23 days since the completion of Temodar and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment

ELIGIBILITY TO PROCEED WITH T CELL INFUSION:

  • Research participant has a released cryopreserved T cell product
  • Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive
  • Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias
  • Research participant does not have a fever exceeding 38.5° Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis
  • Serum total bilirubin does not exceed 2 x normal limit
  • Transaminases does not exceed 2 x normal limit
  • Serum creatinine =< 1.8 mg/dL
  • Research participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell dose
  • Platelet count must be >= 100,000; however, if platelet level is between 75,000-99,000, then T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is >= 100,000
  • Research participants must not require more than 2 mg thrice daily (TID) of dexamethasone during T cell therapy

Exclusion Criteria:

  • Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
  • Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
  • Research participant requires dialysis
  • Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
  • Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
  • Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
  • Research participants with any other active malignancies
  • Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
  • Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
  • Research participants who have confirmed HIV positivity within 4 weeks of enrollment
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02208362


Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Paige Myers-McNamara    626-218-9393    neurosurgerymail@coh.org   
Contact: Paige Myers-McNamara    844-333-4673      
Principal Investigator: Behnam Badie, MD         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Gateway for Cancer Research
Mustang Bio, Inc.
Investigators
Principal Investigator: Behnam Badie, MD City of Hope Medical Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT02208362     History of Changes
Other Study ID Numbers: 13384
NCI-2014-01488 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
13384 ( Other Identifier: City of Hope Medical Center )
R01FD005129 ( U.S. FDA Grant/Contract )
First Submitted: August 1, 2014
First Posted: August 5, 2014
Last Update Posted: September 4, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
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