Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Esophageal Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Within 2 weeks of starting RT, patients undergo CMR, cardiac PET/CT and blood sample collection at baseline, then between fractions 12-17 of RT and at 6 months after completion of RT.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging of the Heart

Positron Emission Tomography

The Ohio State University Comprehensive Cancer Center

Eric D. Miller, MD, PhD

Eric D Miller, MD, PhD

This study assesses for early signs of damage to the heart following chest radiation therapy using both imaging (cardiac magnetic resonance imaging and cardiac positron emission tomography) and changes in blood biomarkers. This study determines if any changes in the heart muscle can be detected either during the course of radiation therapy or shortly thereafter using specialized imaging techniques or blood tests. Cardiac magnetic resonance imaging may be used to help provide information about changes in the heart structure and function following radiation therapy. Positron emission tomography looks at differences in how the heart takes up radioactive sugar which is injected into the vein to assess changes in heart function following radiation therapy. This study may help identify patients at risk of heart issues following radiation therapy to the chest and ultimately help in the development of more effective and safe treatments for cancer in the future.

PRIMARY OBJECTIVES:

I. To evaluate and quantitate early changes in myocardial fibrosis following thoracic radiation therapy (RT).

II. To assess quantitative early changes in myocardial inflammation after thoracic RT.

III. To determine if thoracic RT is associated with early changes in myocardial metabolism as assessed with cardiac positron emission tomography (PET).

SECONDARY OBJECTIVES:

I. To evaluate and quantitate early changes in subclinical myocardial dysfunction after thoracic RT.

II. To determine if thoracic RT is associated with early changes in myocardial metabolism using alternative cardiac PET-derived biomarkers.

III. To evaluate and quantitate early changes in blood-based biomarkers after thoracic RT.

IV. To assess the incidence and severity of cardiac events following completion of thoracic RT.

OUTLINE:

Within 2 weeks of starting RT, patients undergo cardiac magnetic resonance (CMR) imaging, cardiac positron emission tomography (PET)/computed tomography (CT) and blood sample collection at baseline, then between fractions 12-17 of RT and at 6 months after completion of RT.

Imaging and Blood-Based Biomarkers for the Evaluation of Early Signs of Myocardial Injury After Thoracic Radiation Therapy

A Pilot Study to Evaluate Early Signs of Myocardial Injury After Thoracic Radiotherapy Using Imaging and Blood-Based Biomarkers

To identify the presence of cardiac fibrosis as assessed by cardiac magnetic resonance-derived ECV during and shortly after RT.

To identify the presence of cardiac magnetic resonance-derived cardiac inflammation using T2 mapping during and shortly after RT.

To identify changes in myocardial metabolism measured as standardized uptake value (SUV) max during and shortly after RT using myocardial PET.

Biomarkers including serum troponin, N-terminal Pro Brain-type Natriuretic Peptide (NT-proBNP), C-reactive protein, carboxy-terminal propeptide of procollagen type I (PICP), and amino-terminal propeptide of procollagen type I (PINP) will be measured.

Ohio State University Comprehensive Cancer Center

Principal Investigator

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Recurrence

Osteosarcoma

Neuroblastoma

Disease Attributes

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Gaucher Disease Type 2

Neuroepithelioma

Soft Tissue Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Vaccines

Immunologic Factors

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate IV daily on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2.

GD2CART: Patients receive GD2CART cells IV on day 0.

Patients also undergo ECHO, MUGA or cardiac MRI scan during screening, blood sample collection throughout the trial, and tumor biopsies as clinically indicated. In addition, patients undergo standard imaging scans throughout the trial.

Biopsy

Echocardiography

Fludarabine Phosphate

GD2-CAR-expressing Autologous T-lymphocytes

Imaging Technique

Multigated Acquisition Scan

Rosandra N Kaplan

This phase I trial investigates the side effects and determines the best dose of an immune cell therapy called GD2CART, as well as how well it works in treating patients with osteosarcoma or neuroblastoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this trial will come from the patient and will have a new gene put in them that makes them able to recognize GD2, a protein on the surface of tumor cells. These GD2-specific T cells may help the body's immune system identify and kill GD2 positive tumor cells.

PRIMARY OBJECTIVES:

I. Determine the feasibility of producing T cells modified to express a GD2-specific chimeric antigen receptor (GD2-CAR-expressing autologous T-lymphocytes \[GD2CART\]) meeting established release criteria using a dasatinib containing culture platform and retroviral vector in the Miltenyi CliniMACS Prodigy (Registered Trademark) system.

II. Determine the safety and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) via administration of escalating doses of autologous GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma following cyclophosphamide-fludarabine based lymphodepletion.

III. Determine clinical activity in a preliminary fashion of autologous GD2CART in children and young adults with relapsed, refractory osteosarcoma and neuroblastoma.

SECONDARY OBJECTIVES:

I. Measure persistence of adoptively transferred GD2CART and correlate this with antitumor effects.

II. If unacceptable toxicity occurs that is possibly, probably, or likely related to GD2CART, assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.

III. Describe the feasibility and tolerability of a second infusion of GD2CART in select patients.

EXPLORATORY OBJECTIVES:

I. Compare persistence of GD2CART administered in this trial to that observed in a previous trial using GD2.OX40.28.z.iCasp9 CAR T cells (NCI 14-C-0059) and assess features of the T cell product and the expanded T cells in vivo that correlate with persistence.

II. Conduct exploratory studies measuring levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.

III. Explore GD2 expression in patients with neuroblastoma and osteosarcoma, including patients who have previously received anti-GD2 antibodies, from tissue and/or bone marrow samples at study entry and if available, after cell infusion.

OUTLINE: This is a dose-escalation study of GD2CART followed by a dose-expansion study.

LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) daily on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2.

GD2CART: Patients receive GD2CART cells IV on day 0.

Patients also undergo echocardiogram (ECHO), multigated acquisition scan (MUGA) or cardiac magnetic resonance imaging (MRI) scan during screening, blood sample collection throughout the trial, and tumor biopsies as clinically indicated. In addition, patients undergo standard imaging scans throughout the trial.

After completion of study treatment, patients are followed up three times weekly until day 14, twice weekly until day 28, at months 2, 3, 6, 9, and 12, every 3 months until the end of the second year, then annually for up to 10 years.

Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial

GD2-CAR PERSIST: Production and Engineering of GD2-Targeted, Receptor Modified T Cells (GD2CART) for Osteosarcoma or Neuroblastoma to Increase Systemic Tumor Exposure

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Associations between biomarkers and chimeric antigen receptor (CAR) persistence will be assessed by regression. The exact statistical model will depend on the observed responses which might not be linearly related to biomarkers but could show logistic or other association. Relationships of biomarkers to outcomes (overall survival, progression free survival) will be assessed by Cox regression using baseline measurements as predictors. The proportional hazards assumption will be checked retrospectively.

Will measure levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.

Tumor and/or normal tissue will be obtained from archival sample, tissue or tumor biopsy, or any clinically indicated surgeries. Bone marrow aspirations will be conducted in all patients with neuroblastoma. In patients with osteosarcoma, bone marrow aspirations will be conducted only if clinically indicated, i.e. known bone marrow involvement.

Success will be defined by manufacturing and expansion of GD2CART to satisfy the targeted dose level and meet the requirements of the Certificate of Analysis. Specifically, dose escalation will proceed if 3 or more of the first 3 to 6 patients in a dose level are able to produce adequate cells for evaluation.

Safety of GD2CART will be by the incidence and severity of dose limiting toxicities (DLTs), treatment emergent AEs (TEAEs), serious adverse events (SAEs), laboratory abnormalities, changes in vital signs, and changes in physical examination following infusion of GD2CART cells.

Simon's two stage design will be used to evaluate the clinical benefit of GD2CART after conditioning lymphodepletion chemotherapy in two groups of patients: children and young adults with recurrent, refractory osteosarcoma and neuroblastoma.

Persistence of GD2CART and correlation with tumor regression and sustained clinical benefit will be assessed. Persistence will be defined as the duration of time that GD2CART cells can be detected above the background rate (baseline measure) as measured by polymerase chain reaction (PCR). The persistence will be compared between the different response statuses (responders versus non-responders) using a t-test allowing for unequal variance.

The toxicity is defined to be reversed or resolved when the toxicity grading has resolved to grade 2 or below. The resolution of toxicity will be summarized descriptively.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Imaging and Blood-Based Biomarkers for the Evaluation of Early Signs of Myocardial Injury After Thoracic Radiation Therapy	NCT05717998	Lung Non-Small ... GastroEsophagea... Esophagus Cance...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Positron Emissi...	18 Years -	Ohio State University Comprehensive Cancer Center
Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial	NCT04539366	Recurrent Neuro... Recurrent Osteo... Refractory Neur... Refractory Oste...	Biopsy Biospecimen Col... Cyclophosphamid... Echocardiograph... Fludarabine Pho... GD2-CAR-express... Imaging Techniq... Magnetic Resona... Multigated Acqu...	- 40 Years	National Cancer Institute (NCI)

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