Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Diseases

Glioma

Central Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Adjuvants, Immunologic

Immunologic Factors

All patients will receive the full TVI-Brain-1 treatment.

Following surgery, tumor tissue is used to generate a cancer vaccine. Patients are vaccinated with neutralized cells to initiate an immune response. Following vaccinations, the patient's white blood cells are collected, the white blood cells are stimulated and expanded, and are then reinfused into the patient's blood.

TVI-Brain-1

Gary Wood, Ph.D.

TVI-Brain-1 is an experimental treatment that takes advantage of the fact that your body can produce immune cells, called 'killer' white blood cells that have the ability to kill large numbers of the cancer cells that are present in your body. TVI-Brain-1 is designed to generate large numbers of those 'killer' white blood cells and to deliver those cells into your body so that they can kill your cancer cells.

The TVI-Brain-1 treatment involves several steps. First, the patient's cancer will be surgically removed to provide cells for the vaccine. Second, the patient will be vaccinated with the vaccine formulation. Third, the patient's blood will be filtered for killer T cell precursors which will then be cultured and stimulated to reach a higher (killer) activity level. Fourth, the activated cells will be infused into the patient's bloodstream so that they will be able to attack the cancer.

Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma

Phase 2 Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma

To assess the efficacy of TVI-Brain-1 on patients to evaluate progression free survival. MRI data is used to evaluate tumor progression; success is defined if a patient is still alive and has \< 25 % increase in Tumor volume in MRI collected at 6 month timepoint.

All patients will be followed until death or the end of the study to measure overall survival.

Toxicity will be assessed throughout the study by recording clinical symptoms, performing physical examinations, measuring vital signs and performing clinical laboratory tests, including complete blood counts and differentials, blood chemistries and autoimmune profiles.

Time to progression is defined date of evidence of increase in tumor volume as evaluated by review and analysis of imaging, using MacDonald Criteria in review of serial MRI's taken at specific timepoints

Time to progression is defined as assessed by neurologists and radiologists evaluation of time to worsening of patient's neurological status and/or increase in tumor volume measurements as evaluated by review and analysis of serial physical exams and MRI's taken at specific timepoints

Skin Test using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.

Evidence of a Resulting wheal or flare reaction from sub-cutanous injection of test will be evaluated in each patient

Quality of life data using the FACT-Br score tabulation from responses on validated tool

TVAX Biomedical

Adverse events were collected at all clinic visits through evaluation of blood chemistry and hematology labs, vital sign measurements, physical exams, and direct patient questioning.

All patients will receive the full TVI-Brain-1 treatment.

TVI-Brain-1: Following surgery, tumor tissue is used to generate a cancer vaccine. Patients are vaccinated with neutralized cells to initiate an immune response. Following vaccinations, the patient's white blood cells are collected, the white blood cells are stimulated and expanded, and are then reinfused into the patient's blood.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Recruitment was stopped to allow a change in protocol design. Some positive clinical effects were observed but this study design treated Subjects whose cancers have progressed following surgery, radiotherapy, and temozolomide chemotherapy and therefore have immune systems that are too compromised to allow maximal benefit from the use of TVI-Brain-1. Study #008 is changed to treat newly diagnosed Subjects with healthy immune systems and minimal residual disease.

Michael E. Salacz,MD and David Tran,MD, PH.D

Progression of Disease

Overall Survival

Toxicity was assessed throughout the study by recording clinical symptoms, physical examinations, vital signs, clinical laboratory tests, including blood counts and differentials, blood chemistries and autoimmune profiles. Patients were monitored for toxicities during the study and for one month following removal from the study for any reason.

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Time to Progression of Tumor Per MRI

Objective Response Rate

Delayed-type Hypersensitivity (DTH) Skin Testing

Quality of Life as Measured by FACT-Br Tool Score

Overall Study

Ependymoma

Disease Attributes

Activated T cells (ATC) administered intravenously at one timepoint

Activated T cells

Kortnee Calkins

Jethro Hu, MD

Justin Darrah, MD

Ray Chu, MD

Chirag Patil, MD

Jeremy Rudnick, MD

The purpose of this study is to examine the use of activated T cells (ATCs) to assess the safety and tolerability of autologous activated T cells, as measured by the number of Grade 3 or higher toxicities, the number of serious adverse events, and treatment-related toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 5, to find the maximum tolerated dose. The secondary objectives include evaluating the rate of overall survival, rate of progression-free survival, health-related quality of life parameters, overall response rate, immune response, and tumor stem cell antigen expression.

Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma

A Phase I Trial of Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma

Recorded and graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAEs) Version 5

Measured by change in the Functional Assessment of Cancer Therapy - Brain (FACT-Br) survey score. The FACT-Br total score has a range of 0-200 and higher scores indicate better quality of life

Percentage of patients showing either partial response or complete response, in patients with subtotal resection, will be measured using Magnetic Resonance Imaging (MRI) and Immunotherapy Response Assessment in Neuro-Oncology (iRANO) Response Criteria

Assessed by cytotoxic T cell activity in vitro pre- vs post-infusion.

Assessed by quantitative PCR for expression of CD133, housekeeping genes, and tumor associated antigens (including HER2, TRP-2, gp100, MAGE-1, IL13Rα2, AIM-2).

Kairos Pharma

Jeremy Rudnick, M.D

Co-Director, Neuro-Oncology

Osteosarcoma

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Gaucher Disease Type 2

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Antibodies

Sargramostim

Aldesleukin

Antibodies, Bispecific

Immunoglobulins

Muromonab-CD3

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.

IL-2

GD2Bi-aATC

GM-CSF

laboratory evaluations of immune responses

Holly Davis

Maxim Y. Yankelevich, MD

Diana Gomez, MPH

Shakeel Modak, M.D.

Alexandar Chou, M.D.

Daniel (Trey) Lee, MD

Maxim Yankelevich

Previous research has demonstrated that investigators can coat (arm) T cells with a special molecule called GD2 bispecific antibody that will help T cells recognize neuroblastoma and osteosarcoma cells and kill them. This bispecific antibody recognizes GD2, a protein found on almost all neuroblastoma and osteosarcoma cells. The investigators put the GD2 bispecific antibody on T cells and give large numbers of these T cells back to patients. The investigators think that these T cells may have a better chance of killing GD2 expressing tumor cells when they are armed with GD2 bispecific antibody. This trial studies the side effects and best dose of activated T cells armed with GD2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other GD2-positive solid tumors.

PRIMARY OBJECTIVES:

I. To perform a phase I dose-escalation study in patients with recurrent or refractory neuroblastoma (NB) and other GD2-positive tumors to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) for anti-CD3 x hu3F8 bispecific antibody (GD2Bi)-armed activated T cells (aATC) infused twice a week for a total of eight infusions in combination with daily IL-2 (300,000 IU/m\^2/day) and GM-CSF (250 ug/m\^2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10\^6 cells/kg/infusion dose levels.

II. To conduct a phase II clinical trial to explore efficacy and confirm the toxicity profile of GD2Bi-aATC combined with IL-2 and GM-CSF in a phase II expansion cohort of 22 patients with neuroblastoma (NB) using MTD determined in the phase I.

SECONDARY OBJECTIVES:

I. Evaluate immune responses in the phase I/II trial by sequential monitoring of anti-NB cytotoxicity of peripheral blood lymphocytes and IFN-gamma EliSpots directed at NB lines.

II. To evaluate persistence of aATC in the blood and tumor biopsies by staining for murine IgG2a to confirm trafficking of armed T cells to tumor.

III. To conduct exploratory study of (18F FDG) positron emission tomography (PET)/computed tomography (CT) after armed ATC infusions in selected patients with PET/CT measurable soft tissue and skeletal lesions.

OUTLINE: This is a phase I, dose-escalation study of OKT3/humanized 3F8 bispecific antibody-aATC followed by a phase II study.

Patients receive IL-2 subcutaneously (SC) daily on days -2 to 35, sargramostim SC twice weekly for 4 weeks, and OKT3/humanized 3F8 bispecific antibody-aATC intravenously (IV) over 30 minutes twice weekly for 4 weeks.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.

Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma

Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study

Safety of GD2Bi-aATC infusions is evaluated to determine MTD

Objective response rate to GD2Bi-aATC infusions

In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes

National Cancer Institute (NCI)

University of Virginia

Principal Investigator

Anaplastic Astrocytoma

Cancer vaccine plus immune adjuvant Biological/vaccine Other

Tumor tissue is used for cancer vaccine. Following vaccinations, white blood cells are collected, stimulated and expanded, and are then reinfused. The infusion is followed by a course of low-dose IL-2.

Cancer vaccine plus immune adjuvant

Michael Salacz, M.D.

TVI-Brain-1 involves several steps. First, the patient's cancer will be surgically removed to provide cells for the vaccine. Second, the patient will be vaccinated twice with those cells and GM-CSF. Third, the patient's blood will be filtered for white cells which will then be cultured and stimulated to reach a higher (killer) activity level. Fourth, the activated white blood cells will be infused into the patient's bloodstream so that they will be able to attack the cancer. Finally, the entire process starting with vaccination will be repeated, for a total of two rounds of therapy.

Phase I/II Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma

To determine the relative toxicity (safety) of vaccinating recurrent grade IV glioma patients four times with live, attenuated cancer cells combined with granulocyte-macrophage colony-stimulating factor (GM-CSF). Toxicity will be assessed following delivery of each treatment component.

The potency of the modified vaccination regimen will be assessed by measuring immune responses following each vaccination. The study is designed to determine whether vaccinating recurrent grade IV glioma subjects four times with attenuated cancer cells stimulates more powerful immune responses than vaccinating subjects twice. Clinical effects also will be measured to determine whether the treatment causes the cancer to regress.

Systematic assessments by questionnaires and completion of CRF at each scheduled visit

Biological/Vaccine: Cancer vaccine plus immune adjuvant, plus activated white blood cells

Age, Continuous

United States

Latvia

Region of Enrollment

Gary Wood PhD

Number of participants that completed treatment protocol

Number of Participants Experiencing the Incidence of Grade One or Higher Adverse Events

Cancer vaccine plus immune adjuvant Biological/vaccine Other

Cancer vaccine plus immune adjuvant: Tumor tissue is used for cancer vaccine. Following vaccinations, white blood cells are collected, stimulated and expanded, and are then reinfused. The infusion is followed by a course of low-dose IL-2.

Ten patients developed an immunological response to their tumor as indicated by the delayed type hypersensitivity immune test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma	NCT01290692	Grade IV Glioma Grade IV Astroc... Glioblastoma Mu...	TVI-Brain-1	18 Years -	TVAX Biomedical
Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma	NCT05341947	Recurrent Gliob...	Activated T cel...	18 Years -	Cedars-Sinai Medical Center
Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma	NCT02173093	Disseminated Ne... Recurrent Neuro...	IL-2 GD2Bi-aATC GM-CSF laboratory eval...	13 Months - 29 Years	University of Virginia
Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma	NCT01290692	Grade IV Glioma Grade IV Astroc... Glioblastoma Mu...	TVI-Brain-1	18 Years -	TVAX Biomedical
Phase I/II Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma	NCT01081223	Glioma High Grade Astr... Glioblastoma Mu...	Cancer vaccine ...	18 Years -	TVAX Biomedical

Spots Global Cancer Trial Database for activated t cells