Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Meningioma

Astrocytoma

Ependymoma

Oligodendroglioma

Gliosarcoma

Solitary Fibrous Tumors

Hemangiopericytoma

Neoplasms, Fibrous Tissue

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Anaplastic Ependymoma

Embryonal Tumor With Multilayered Rosettes

Neuroepithelioma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Aldesleukin

Immunomodulating Agents

Glucocorticoids

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients receive intratumoral GRm13Z40-2 therapeutic allogeneic lymphocytes over 10 minutes on days 1 and 3 and intratumoral aldesleukin over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.

therapeutic allogeneic lymphocytes

aldesleukin

laboratory biomarker analysis

positron emission tomography

Behnam Badie

RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Donor T cells that are treated in the laboratory may be effective treatment for malignant glioma. Aldesleukin may stimulate the white blood cells to kill tumor cells. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best way to give therapeutic donor lymphocytes together with aldesleukin in treating patients with stage III or stage IV malignant glioma.

PRIMARY OBJECTIVES:

I. To assess the safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy in research participants with recurrent or refractory/ progressive malignant glioma (WHO Grades 3 or 4).

II. To assess the safety of convection enhanced delivery (CED) of recombinant human Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer.

SECONDARY OBJECTIVES:

I. To investigate the ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG) positron emission tomography PET to image GRm13Z40-2 CTL's in research participants.

II. To study the impact of concurrent dexamethasone administration on the tempo and magnitude of T cell allograft rejection responses in treated research participants by tracking the frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral blood samples.

III. To evaluate ganciclovir administration for ablating transferred GRm13Z40-2 in vivo should significant graft-mediated toxicities be encountered.

OUTLINE: Patients receive GRm13Z40-2 therapeutic allogeneic lymphocytes intratumorally (IT) over 10 minutes on days 1 and 3 and aldesleukin IT over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for at least 15 years.

Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

City of Hope Medical Center

Disease Attributes

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 of courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Undergo electric field therapy using Optune device

Electric Field Therapy

NovoTTF-200A Device

Quality-of-Life Assessment

Study Coordinator

Santosh Kesari, MD, PhD

Seema Nagpal, MD

Minesh P. Mehta, MD

Erin Dunbar, MD

Priya Kumthekar, MD

Jeffrey Raizer, MD

Karan Dixit, MD

Orin Bloch, MD

James P. Chandler, MD

Sean Grimm, MD

Richard A. Peterson, MD

Arati S. Desai, MD

The purpose of this research study is to determine the effects bevacizumab (the study drug) combined with Optune (the study device) tumor treatment field therapy has on meningiomas. Bevacizumab is considered investigational because the US Food and Drug Administration (FDA) has not approved its use for the treatment of meningiomas. The study drug is a medication that blocks the growth of new blood vessels. It is thought that the study drug may interfere with the growth of new blood vessels and therefore might stop tumor growth, and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels. Optune is also considered investigational because the US FDA has not approved its use for the treatment of meningiomas. Optune is a device that the patient will wear and use for at least 18 hours of each day. It delivers alternating electrical current to the patient's brain tumor and by doing so interrupts a process called mitosis. Mitosis needs to occur in order for cell division to occur and allows tumors to grow. By slowing this process, we hypothesize that meningioma growth may also be slowed.

PRIMARY OBJECTIVES:

I. To determine progression free survival (PFS) for 6 months (PFS-6) in patients with recurrent or progressive meningioma.

SECONDARY OBJECTIVES:

I. To determine overall survival (OS). II. To determine tumor response rate (TRR). III. To assess quality of life with treatment (QOL) using Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 of courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma

A Phase 2, Single Arm, Multi-center, Open Label Trial Combining Optune With Concurrent Bevacizumab in the Setting of Recurrent or Progressive Meningioma

Determine the efficacy of combination therapy of bevacizumab and Optune (TTF) as assessed by Progression Free Survival at 6 months

OS will be defined from the time of registration to death and will be assessed for up to 2 years.

Imaging (MRI or CT scan) will assess radiographic response in terms of complete response, partial response, stable disease, and progressive disease. The iRANO criteria will be used for response assessment.

To assess QOL with treatment the Functional Assessment of Cancer Therapy-Brain version 4.0 (FACT-Br) questionnaire will be administered.

NovoCure Ltd.

National Cancer Institute (NCI)

Northwestern University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2	NCT01082926	Anaplastic Astr... Anaplastic Epen... Anaplastic Meni... Anaplastic Olig... Brain Stem Glio... Ependymoblastom... Giant Cell Glio... Glioblastoma Gliosarcoma Grade III Menin... Meningeal Heman... Mixed Glioma Pineal Gland As... Brain Tumor	therapeutic all... aldesleukin laboratory biom... positron emissi...	18 Years - 70 Years	City of Hope Medical Center
Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma	NCT02847559	Anaplastic (Mal... Atypical Mening... Grade II Mening... Grade III Menin... Recurrent Menin... Supratentorial ...	Bevacizumab Electric Field ... NovoTTF-200A De... Quality-of-Life...	18 Years -	Northwestern University

Spots Global Cancer Trial Database for grade iii meningioma