Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Pembrolizumab

Autoantibodies

Avelumab

Nivolumab

Atezolizumab

Ipilimumab

Antineoplastic Agents, Immunological

All enrolled patients must have been diagnosed with a cancer potentially treatable with ipilimumab, nivolumab, pembrolizumab, atezolizumab or avelumab, alone or in combination, per standard protocol.

Treatment with approved immune checkpoint inhibitors, namely ipilimumab, nivolumab, pembrolizumab, atezolizumab and avelumab, alone or in combination, administered per standard protocol.

Treatment with immune checkpoint inhibitors.

Patients will undergo ordinary blood tests obtained at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE.

Blood tests.

Iñigo Les Bujanda, MD PhD

Inés Pérez Francisco

The aim of this study is to assess the effectiveness of a battery of autoantibodies to predict the occurrence of immune-related adverse events (irAEs) in patients with cancer who will be treated with immune checkpoint inhibitors (ICIs) per standard protocol.

Introduction: Treatment with ICIs is leading to a remarkable improvement in the prognosis of several types of cancer. However, the expansion of these drugs in the field of oncology is also causing the emergence of a large diversity of irAEs, whose optimal prevention and management are still to be clarified. Nowadays, there is a growing need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs.

Purpose: To assess the effectiveness of a battery of autoantibodies available in a laboratory of autoimmunity to predict the occurrence of irAEs in patients with cancer who will be treated with ICIs per standard protocol.

Methods: A multicenter prospective observational cohort study was designed to include a total of 221 patients diagnosed with cancer amenable to treatment with ICIs. During a period of 48 weeks, patients will be controlled in the oncology outpatient clinics of five university hospitals with accredited experience in the management of immunotherapy. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. Considering a proportion of irAEs and losses to follow-up of 25% and 5% respectively, a sample size of 221 patients was calculated to estimate an expected sensitivity of the autoantibody battery of 0.90 with a 95% confidence interval not lower than 0.75. All the participants will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE. Both ordinary and extraordinary samples will be frozen and stored in the biobank of each participating hospital in the form of serum and buffy coat. Once the whole cohort reaches the 24th week (intermediate analysis) and the 48th week (definitive analysis), all the samples will be centralized in the same autoimmunity laboratory for the determination of the autoantibody battery. A predictive model of irAEs will be constructed with the autoantibodies together with other potential risk factors of immune-mediated toxicity.

Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)

Prediction of Immune-related Adverse Events Induced by Anti-CTLA4 and Anti-PD1/PDL1 Drugs by Means of a Battery of Autoantibodies. A Multicenter Prospective Observational Cohort Study

All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

An irAE was defined as any symptom, sign, syndrome or disease attributable to an immune activation mechanism during an ongoing treatment with an ICI or a combination of ICIs, provided that an infectious cause and/or tumor progression have been ruled out.

Time in months from the initiation of therapy with ICIs until the occurrence of an irAE or until the date of the last follow-up.

Time in months from the initiation of therapy with ICIs until the date of proven tumor progression or until the date of the last follow-up.

Time in months from the initiation of therapy with ICIs until the date of patient's death or until the date of the last follow-up.

Positive conversion of the autoantibody battery after the initiation of therapy with ICIs.

Hospital de Basurto

Hospital Donostia

Complejo Hospitalario de Navarra

Hospital Galdakao-Usansolo

Hospital Universitario Araba

Principal Investigator

Nervous System Diseases

Immune System Diseases

Infections

Rare Diseases

Epilepsy

Drug Resistant Epilepsy

Autoimmune Diseases

Encephalitis

Seizures

Epilepsies, Partial

Limbic Encephalitis

Autoimmune Diseases of the Nervous System

Brain Diseases

Central Nervous System Diseases

Neurologic Manifestations

Neuroinflammatory Diseases

Virus Diseases

Central Nervous System Viral Diseases

Communicable Diseases

Central Nervous System Infections

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Neurodegenerative Diseases

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

Immunologic Factors

IVIG 2 mg/kg in two divided doses with placebo crossover

IVIG

Charles M. Epstein, M.D.

The purpose of the initial screening study is to find out if immune problems are an unrecognized cause of epilepsy in some patients. This study consists of a single blood sample, which will be tested for possible immune abnormalities. If enough patients are found who show immune abnormalities, those patients who are still having uncontrolled seizures will be invited to participate in a study of immune treatment with a compound called intravenous immunoglobulin (IVIG).

The study hypothesis is that a significant proportion of the young-onset, refractory, image-negative, partial-onset epilepsy population have an underlying autoimmune disorder, and many of these patients will respond to immune therapies, including IVIG.

At present, the importance of immune abnormalities in causing epilepsy, and the proper treatment when they are found, are both poorly understood. The investigators hope that this study will help us understand the cause of some cases that are difficult to treat.

The study is divided into two phases:

Phase I: The investigators will screen for evidence of neuronal nuclear, cytoplasmic, and cell surface autoantibodies in our population of new onset refractory, imaging-negative young adult epilepsy patients. This part of the study involves obtaining a single blood sample, equal to about 2 teaspoons.

Phase 2: If a sufficient number of cases are identified, a double-blind crossover study of IVIG treatment will be performed in these patients.

IVIG Treatment for Refractory Immune-Related Adult Epilepsy

neuronal nuclear, cytoplasmic, and cell surface autoantibodies

Baxter Healthcare Corporation

Emory University

Professsor of Neurology - Divsion of Epilepsy

IVIG

IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover

No AE's.

All Subjects

IVIG

IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Study was terminated early. Subject eligibility for phase 2 not available.

Dr. Charles M. Epstein

No analysis occurred and study was terminated early due to subject numbers not eligible for the 2nd phase of the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba
IVIG Treatment for Refractory Immune-Related Adult Epilepsy	NCT01545518	Epilepsy, Crypt... Epilepsy, Parti... Seizure Disorde... Autoimmune Dise... Limbic Encephal...	IVIG	18 Years - 50 Years	Emory University
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba
Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC)	NCT03868046	Cancer Metastatic Canc... Solid Organ Can...	Treatment with ... Blood tests.	16 Years - 99 Years	Hospital Universitario Araba

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