Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma
|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.|
|ClinicalTrials.gov Identifier: NCT04661384|
Recruitment Status : Recruiting
First Posted : December 10, 2020
Last Update Posted : January 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Leptomeningeal Metastases||Biological: IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes||Phase 1|
I. Examine and describe the safety and feasibility of IL13Ralpha2-specific hinge-optimized 41BB-co-stimulatory CAR truncated CD19-expressing autologous T-lymphocytes (IL13Ralpha2-CAR T cells) through intracerebroventricular (ICV) delivery as adjuvant therapy in participants with:
Ia. IL13Ralpha2+ leptomeningeal disease from glioblastoma (arm 1). Ib. IL13Ralpha2+ leptomeningeal disease from ependymoma or medulloblastoma (arm 2).
II. Determine the activity of IL13Ralpha2-CAR T cells based on survival rate at 3 months for both arms.
I. Describe persistence, expansion and phenotype of endogenous and IL13Ralpha2-CAR CAR T cells in peripheral blood (PB), tumor cyst fluid (TCF) and cerebral spinal fluid (CSF), when available.
II. Describe cytokine levels in PB, TCF, and CSF (when available) over the study period for each arm.
III. Estimate the rate of disease response by Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria by study arm where an active response is defined as stable disease or better.
IV. Estimate rate of progression free survival at 3 months by study arm. V. Estimate rate of overall survival (OS) at 3 months by study arm.
VI. In study participants who undergo post therapy biopsy/resection or autopsy:
VIa. Evaluate IL13Ralpha2-CAR T cell persistence in the tumor tissue and the location of the IL13Ralpha2-CAR T cells with respect to the infusion site.
VIb. Evaluate IL13Ralpha2 antigen on tumor tissue pre- and post-CAR T cell therapy.
VII. Use biomathematical modeling of tumor growth to evaluate benefit of treatment.
Patients receive IL13Ralpha2-CAR T cells ICV over 5 minutes on day 1. Treatment repeats every 7 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles per the discretion of the principal investigator.
After completion of study treatment, patients are followed up at 30 days, months 3, 6, 9, 12, and then yearly for up to 15 years.
|Study Type :||Interventional|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study to Evaluate IL13Rα2-Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma, Ependymoma or Medulloblastoma|
|Estimated Study Start Date :||February 15, 2021|
|Estimated Primary Completion Date :||December 15, 2022|
|Estimated Study Completion Date :||December 15, 2022|
Experimental: Treatment (IL13Ralpha2-CAR T cells)
Patients receive IL13Ralpha2-CAR T cells ICV over 5 minutes on day 1. Treatment repeats every 7 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Biological: IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes
Other Name: Autologous IL13(EQ)BBzeta/CD19t+ TCM-enriched T Cells
- Incidence of adverse events [ Time Frame: Up to 15 years ]Will be assessed using the NCI's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Overall survival [ Time Frame: At 3 months ]
- CAR T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) [ Time Frame: Up to 4 cycles (4 weeks) ]Measured by absolute number per ul by flow.
- Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) [ Time Frame: Up to 4 cycles (4 weeks) ]Measured by absolute number per ul by flow.
- Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) [ Time Frame: Up to 4 cycles (4 weeks) ]Measured by absolute number per ul by flow.
- Cytokine levels in PB, TCF and CSF [ Time Frame: Up to 4 cycles (4 weeks) ]
- Disease response [ Time Frame: Up to 15 years ]Measured by Response Assessment in Neuro-Oncology Criteria (RANO LM).
- Time to progression [ Time Frame: Up to 15 years ]Progression defined by RANO LM criteria.
- Overall survival [ Time Frame: Up to 15 years ]
- CAR T and endogenous cells detected in tumor tissue [ Time Frame: Baseline ]Detected in tumor tissue by immunohistochemistry (IHC).
- IL13Raphs2 antigen expression levels in tumor tissue. [ Time Frame: Baseline ]Descriptive statistics will be provided.
- Biomathematical Modeling of tumor growth [ Time Frame: 15 years ]Will assess tumor growth parameter based on serial brain magnetic resonance imaging (MRI)s. Tumor volumes will be computed for each MRI study beginning with the pre-surgical MRI and will be used to compute growth rates, measured as change in tumor volume over time. Tumor volumes will be derived from T1- and T2-weighted MRI sequences. Growth rates will be compared prior to, during, and following CAR T-cell treatment for 1) each individual patient and 2) averaged for each dose level.
- Biomathematical Modeling of perfusion/diffusion [ Time Frame: 15 years ]Will assess perfusion/ diffusion parameter based on serial brain magnetic resonance imaging (MRI)s. Perfusion and diffusion analysis will include the blood plasma-tissue rate transfer constant (Ktrans), cerebral blood volume (vp), contrast accumulation rate (lambda), and the apparent diffusion coefficient (ADC). Perfusion/diffusion analysis will be derived from T1-weighted dynamic contrast enhancement (DCE), T2-weighted dynamic susceptibility (DSC), and diffusion weighted imaging (DWI) sequences. The mean value of the perfusion/diffusion parameters from the contrast-enhancing lesion volume will be extracted for each MRI study.
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): NCT04661384
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Lisa A. Feldman 626-256-4673 ext 89393 firstname.lastname@example.org|
|Principal Investigator: Lisa A. Feldman|
|Principal Investigator:||Lisa A Feldman||City of Hope Medical Center|