Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Bilingual (English and Spanish speaking) patients will be recruited from the clinical service of the Department of Neurosurgery of MSK. All patients on the Neurosurgery service scheduled to undergo a resection of a tumor in or adjacent to the primary language areas will be screened to participate in this study.

The study will be performed in concert with patient's regularly scheduled clinical care for his/her brain tumor. Clinical care (which will be performed whether or not the patient participates in the current study) will include: 1) pre-operative routine (anatomical) MRI and fMRI, 2) the surgery to remove the tumor, 3) intra-operative cortical stimulation to identify the essential motor and/or language areas. It should be stressed that neither the brain tumor surgery, nor the intra-operative cortical mapping will be changed in any way from routine practice.

Normal, healthy volunteers who express interest in participation and who meet the eligibility criteria will be recruited for this study. It is anticipated that healthy volunteers will mostly consist of medical professionals. They will consist of 10 monolinguals (defined as native English speakers), 10 early bilinguals (defined as acquiring proficiency in the second language before 10 years of age), and 10 late bilinguals (defined as acquiring proficiency in the second language after 10 years of age).

For patients only prior to MRI scans.

The MAE contains eleven subtests in five categories which may be used to assess both languages in bilinguals and the participant's primary language in monolinguals: Oral Expression, Spelling, Oral Verbal Understanding, Reading, and Rating Scales. Subtests are scored for accuracy of individual items on a three-point scoring system (0, 1, 2). Contained within these domains are The Token Test, Aural Comprehension of Words and Phrases and Visual Naming which naturally parallel fMRI and direct cortical stimulation behavioral assays already in place for clinical use (phonemic fluency, auditory responsive naming and confrontation naming respectively). The MAE is expected to take under 50 minutes.

Multilingual Aphasia Examination

10 monolingual patients: 2 language paradigms + RS fMRI = 7x3 = 21 minutes 10 early bilingual patients: 2 language paradigms+ RS fMRI = 7x3 = 21 minutes 10 late bilingual patients: 2 language paradigms+ RS fMRI = 7x3 = 21 minutes

Language paradigms + RS fMRI

10 monolingual English volunteers: 2 task language paradigms\* + 1 Resting State fMRI + one anatomical sequence for a total of approximately 25 minutes.

10 late bilingual volunteers: 4 language paradigms (2 English + 2 Spanish) + 1 Resting State fMRI + one anatomical sequence for a total of approximately 39 minutes.

10 early bilingual volunteers: 4 language paradigms (2 English + 2 Spanish) + 1 Resting State fMRI + one anatomical sequence for a total of approximately 39 minutes.

Language paradigms + RS fMRI + one anatomical sequence

Andrei Holodny, MD

Functional magnetic resonance imaging (fMRI) is a non-invasive test used to detect changes in brain activity by taking picture of changes in blood flow. The imaging helps doctors better understand how the brain works. Task based fMRI (TB fMRI) prompts patients to perform different activities (e.g. word selection in a reading task), and is routinely performed on patients in preparation for a Neurological surgery (surgery that involves the nervous system, brain and/or spinal cord). The purpose is to locate areas of the brain that control speech and movement; these images will help make decisions about patient surgeries. However, there are however gaps in knowledge specific to the language areas of the brain, especially for non-English patients and bilingual patients (those who are fluent in more than one language). This study proposes to evaluate if resting state fMRI (RS fMRI) that does not require any tasks, along with a novel way to analyze these images using "graphy theory," may provide more information. Graph theory is a new mathematical method to analyze the fMRI data. The overall goal is to determine if graph theory analysis on RS fMRI may reduce differences in health care treatment and outcomes for non-English speaking and bilingual patients. We hope that the results of this study will allow doctors to perform pre-operative fMRI in patients who do not speak English.

Evaluation of Functional Magnetic Resonance Imaging (fMRI) in Patients Who Speak Two Languages Fluently

Graph Theoretical Analysis of Pre-operative fMRI Data in Bilingual Patients With Brain Tumors

Memorial Sloan Kettering Cancer Center

Diffuse Intrinsic Pontine Glioma

Brain Stem Neoplasms

Infratentorial Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Gaucher Disease Type 2

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Rolling-6 dose escalation design will test GD2-CAR T cells in subjects with H3K27M-mutant DIPG.

GD2CART will be administered in escalating doses on Day 0 in hospitalized subjects with either DIPG or spinal DMG

Intravenously

* Dose Level -1: 3x10\^5 transduced T cells/kg(± 20%)
* Dose Level 1: 1x10\^6 transduced T cells/kg (± 20%)
* Dose Level 2: 3x10\^6 transduced T cells/kg (± 20%)

Intracerebroventricularly, without conditioning lymphodepletion chemotherapy

* Dose Level -1: 10x10\^6 transduced T cells (±20%)
* Dose Level 1: 30x10\^6 transduced T cells (±20%)
* Dose Level 2: 50x10\^6 transduced T cells (±20%)
* Dose Level 3: 100x10\^6 transduced T cells (±20%)

Intracerebroventricularly after administration of conditioning lymphodepletion chemotherapy regimen with cyclophosphamide and fludarabine

* Dose Level -1: 10x10\^6 transduced T cells (±20%)
* Dose Level 1: 30x10\^6 transduced T cells (±20%)
* Dose Level 2: 50x10\^6 transduced T cells (±20%)

Autologous T-Cells transduced with retroviral vector (14g2a-CD8.BB.z.iCasp9) expressing GD2-chimeric antigen receptor

GD2 CAR T cells

Fludarabine 25 mg/m2 per day IV for days -4, -3, -2

Cyclophosphamide 500 mg/m2 per day IV for days -4, -3, -2

Courtney Erickson, RN, BSN

Ashley Jacobs, RN, BSN

Ashley Jacobs

Michelle Monje, MD, PHD

Liora Schultz, MD

Kara Davis, D.O.

Robbie Majzner, MD

Crystal Mackall, MD

Laura Prolo, M.D

Sneha Ramakrishna, MD

Cynthia Campen, MD

Sonia Partap, MD

Paul Fisher, MD

Lindsey Rasmussen, MD

Timothy Cornell, MD

Susan Hiniker, MD

Kristen Yeom, MD

Jasia Mahdi, MD

Brian Scott, MD

Michelle Monje

The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.

Primary Objectives:

* Determine the feasibility of manufacturing autologous T cells transduced with 14g2a-CD8-BBz-iCasp9 retroviral vector expressing GD2 Chimeric Antigen Receptor (GD2CART) for administration in subjects with H3K27M+ diffuse intrinsic pontine glioma (DIPG) or subjects with spinal H3 K27M-mutant diffuse midline glioma (DMG) using a retroviral vector and dasatinib in the Miltenyi CliniMACS Prodigy® system.
* Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of GD2CART in subjects with H3K27M+ DIPG administered after cyclophosphamide/fludarabine-based lymphodepletion regimen using the following dose escalation schedule: DL1: 1e6 transduced T cells/kg; DL2: 3e6 transduced T cells/kg; DL3: 10e6 transduced T cells/kg.
* Assess the safety of the MTD/RP2D of GD2CART in subjects with spinal H3K27M mutant DMG.

Secondary Objectives:

* In a preliminary manner, assess clinical benefit of GD2CART at the RP2D in subjects with H3K27M DIPG or spinal H3 K27M-mutant DMG.
* If unacceptable toxicity occurs that is possibly, probably or likely related to GD2CART, assess the capacity for AP1903, a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG)

Phase 1 Clinical Trial of Autologous GD2 Chimeric Antigen Receptor (CAR) T Cells (GD2CART) for Diffuse Intrinsic Pontine Gliomas (DIPG) and Spinal Diffuse Midline Glioma (DMG)

The percentage of apheresis samples (fresh or frozen) will be determined for each dose cohort.

Severity of dose limiting toxicities (DLTs) following chemotherapy and infusion of GD2CART cells, will be recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at each dose level tested in subjects with H3K27M-mutant DIPG following standard upfront radiation therapy.

Severity of dose limiting toxicities (DLTs) following chemotherapy and infusion of GD2CART cells will be recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in subjects with spinal H3K27M-mutant DMG following standard upfront radiation therapy

Radiographic Response will be evaluated using tumor response criteria:

Complete Response (CR): disappearance on MR of all evaluable tumor and mass effect; stable or improving neurologic examination. If CSF was positive, it must be negative.

Partial Response (PR): ≥ to 50% reduction in tumor size; stable or improving neurologic examination.

Stable Disease (SD): at least stable and maintenance corticosteroid dose not increased, and MR/CT imaging meets neither PR nor PD Progressive Disease (PD): Progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression; OR a \> 25% increase in the bi-dimensional measurement, OR the appearance of a new tumor lesion.

OS is defined as the time from the start of the lymphodepleting chemotherapy preparative regimen to the date of death from any cause

PFS is defined as the time from the start of the lymphodepleting chemotherapy preparative regimen to the date of radiographic progression or death from any cause.

PPS is measured for each subject with DIPG as OS minus PFS, and for each patient with recorded progression as OS minus Time to Progression (TTP)

Resolution of toxicity ≤ grade2, in the event unacceptable toxicity considered possibly, probably or definitely related to GD2CART cells within 72 hours

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Evaluation of Functional Magnetic Resonance Imaging (fMRI) in Patients Who Speak Two Languages Fluently	NCT03496181	Glioma Glioma of Brain Glioma of Spina...	Multilingual Ap... Language paradi... Language paradi...	18 Years -	Memorial Sloan Kettering Cancer Center
GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG)	NCT04196413	Glioma of Spina... Glioma of Brain...	GD2 CAR T cells Fludarabine Cyclophosphamid...	2 Years - 50 Years	Stanford University

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