Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Wounds and Injuries

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Acute Lung Injury

Lung Injury

Transfusion-Related Acute Lung Injury

Lung Diseases

Respiratory Tract Diseases

Thoracic Injuries

Transfusion Reaction

Hematologic Diseases

Acute Respiratory Distress Syndrome

Acute Graft Versus Host Disease

During the Control cohort period patients will have study data collected following transfusion with only conventional PCs for up to 21 days of transfusion support, as clinically indicated in a manner that is consistent with the local standard of care.

During the INTERCEPT phase, patients will receive only INTERCEPT PCs and will have study data collected following transfusion for up to 21 days of transfusion support, as clinically indicated in a manner that is consistent with the local standard of care.

Standard of Care

Edward L Snyder, MD

This study is a prospective, non-randomized sequential cohort, open label, multi-center, non-inferiority, Phase IV surveillance study following transfusion of INTERCEPT PCs. The patient population will be hematology-oncology patients, including those undergoing hematopoietic stem cell transplant (HSCT), expected to require one or more PC transfusions.

For each participating center, the study will start with a brief pilot run-in period with a group of at least 5 patients exposed only to conventional PCs. The purpose of this pilot run-in is to evaluate study logistics and data collection methods within each study center. Data from the pilot phase will be included in the data analysis for the treatment comparison.

After the pilot run-in period, the study will be conducted in two sequential patient cohorts: 1) the Control cohort during which study patients will receive only conventional PCs, and 2) the INTERCEPT cohort during which patients will receive only INTERCEPT PCs. Patient enrollment at each Center will be monitored to target similar numbers of patients into the Control and Test Cohorts within each center. Centers may enroll Control and Test patients in ratios that vary from 2:1 to 1:2 due to institutional requirements to move rapidly to full INTERCEPT implementation, or due to availability issues with either Test or Control components. Within each Center, patient enrollment will be stratified in four categories: (1) chemotherapy only; and by use of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in (2) myeloablative conditioning, (3) non-myeloablative conditioning, and (4) reduced intensity using the Center for International Blood and Marrow Transplant Research (CIBMTR) criteria. Note time from last chemotherapy treatment to first study transfusion should be no more than 30 days. To ensure both Test and Control cohorts have a similar allocation ratio (±10% per category) among the conditioning regimen strata, enrollment caps will be set for the Test cohorts, hence no Test patients will be enrolled to a stratum once the cap for the given stratum is met. Eligible patients will be enrolled in open Test strata sequentially as long as there is sufficient Test PC inventory available. Enrollment may be delayed for the Test cohort if sufficient inventory of Test PCs is not available.

The study will have a pilot run-in period and two sequential cohort groups for each center.

Pilot Run-in Period The pilot run-in period will be conducted in each center with a group of at least 5 patients exposed only to conventional PCs, who provide informed consent for data collection. The purpose of this pilot run-in is to evaluate study logistics and data collection methods within each study center. Data collection will not differ from that required in the two sequential patient cohorts. The data from the pilot phase will be included in the data analysis for the treatment comparisons.

Control and INTERCEPT Cohorts Following the run-in period, the study will be conducted in two sequential cohort periods. Informed consent for data collection without study specific treatment intervention, and under patient confidentiality, will be required for both cohorts prior to any study procedure.

During the Control cohort period, patients will have study data collected following transfusion with only conventional PCs for up to 21 days of transfusion support, as clinically indicated in a manner that is consistent with the local standard of care. During the INTERCEPT phase, patients will receive only INTERCEPT PCs under the same clinical treatment guideline. Patients will be transfused with only study PCs of the assigned treatment type (Conventional or INTERCEPT) in each cohort. Patients enrolled in the Conventional control cohort will be excluded from participating in the study in the INTERCEPT cohort.

Enrollment will be stratified by study center and type of primary disease therapy (chemotherapy only or HSCT with myeloablative, non-myeloablative, or reduced intensity conditioning).

For both cohorts, patients will be supported with study PC transfusions for a maximum of 21 days or until platelet transfusion independence. Patients are considered to have achieved platelet transfusion independence if more than 5 days elapse after exposure to a study PC transfusion. When a patient achieves platelet independence, the patient will have completed the study PC transfusion period (even if they subsequently resume another cycle of platelet support).

For the pilot phase and both cohort periods, all baseline O2 saturation values if available in the medical record should be recorded on eCRF. O2 measures associated with any form of respiratory therapy (except for room air ventilation) should be recorded with the indicated respiratory therapy for each day of therapy. If multiple measures are available in the medical record on a single day, then the worst value will be recorded.

Data collection for all participants will comprise: patient baseline disease characteristics, including primary disease, type of HSCT (auto, allo, cord blood, matched related or matched unrelated) or type of chemotherapy, and medications at study entry and during the study observation period. Patient clinical respiratory status, including, if available, a chest imaging study at baseline and O2 saturation by non-invasive pulse oximetry if available in the medical record prior to the first study transfusion in each cohort period, will also be recorded.

Within each study cohort, patients will be assessed for the primary outcome measure of assisted ventilation for a maximum of 28 days (7 days surveillance following up to of 21 days of study PC transfusion support). Patients with assisted ventilation within the defined timeframe will be further assessed for ARDS using the Berlin criteria by both the Investigator (based on diagnoses documented in the medical record) and the Pulmonary Adjudication Panel. Furthermore, AEs (including TR) will be collected from the primary medical record for 24 hours following the initiation of each study PC transfusion.; SAEs (including ARDS), CSPAEs (Grade 2 or higher AEs affecting the Respiratory System) and mortality will be collected for 7 days post each study transfusion (or until hospital discharge/discontinuation of outpatient platelet transfusion support, whichever is sooner). Investigators will assess the intensity of each AE and SAE and provide their assessment of the relationship of each AE and SAE to the study transfusion. Patients who experience the outcome of assisted ventilation, ARDS, or CSPAEs will be assessed as detailed in Assessment of Pulmonary Adverse Events in the synopsis and in Protocol Section 8.1.

For patients who achieve platelet independence before Study Day 21, AEs will be collected for 24 hours after initiating the last study platelet transfusion prior to platelet independence; the outcome of assisted ventilation, SAEs, ARDS, CSPAEs, and mortality will be collected for 7 days after the last study PC transfusion prior to platelet independence (or until hospital discharge/discontinuation of outpatient platelet transfusion support, whichever is sooner).

For patients who require more than 21 days of PC transfusion support, AEs will be recorded for up to 24 hours after the initiation of the last platelet transfusion up to and including Day 21; the outcome of assisted ventilation, SAEs, ARDS, CSPAEs, and mortality will be collected for up to a maximum of 28 days (7 days after up to 21 days of platelet transfusion support),7 days after initiating the last study transfusion within the 21-day study transfusion period (or until hospital discharge/discontinuation of outpatient platelet transfusion support, whichever is sooner). The lowest daily O2 saturation values in the medical record will be recorded on the eCRF as well.

Study-specific research personnel will review the patient medical record and record study outcomes on electronic Case Report Forms (eCRF). The intensity of AEs and SAEs will be graded according to the most recent version of the Common Terminology Criteria for Adverse Events (CTCAE) classification system. TR will also be assessed following the CDC National Healthcare Safety Network (NHSN) Biovigilance Component Hemovigilance Module Surveillance Protocol (NHSN Protocol).

A Open Label, Post Marketing Surveillance Study Following Transfusion of INTERCEPT Platelet Components

A Prospective, Open Label, Post Marketing Surveillance Study Following Transfusion of INTERCEPT Platelet Components

For the purposes of this study, assisted mechanical ventilation defined as assisted ventilation started after the initiation of the first study PC and can be administered either by intubation or tight fitting mask with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP or BiPAP) ≥ 5 cm H2O, if PEEP or CPAP information is available. Assisted mechanical ventilation is selected as the primary outcome as it provides an objective measure of severe, clinically significant pulmonary injury. Patients will be assessed for the initiation of assisted ventilation within 7 days after each study PC transfusion.

Time from first study Platelet Component transfusion to onset of treatment-emergent assisted mechanical ventilation.

Adverse Events occurring within 24 hours after the initiation of a study PC transfusion.

Transfusion Reactions occurring within 24 hours after the initiation of a study PC transfusion.

Serious Adverse Events occurring within 7 days after each study PC transfusion

Acute Respiratory Distress Syndrome occurring within 7 days after each study PC transfusion

Clinically Serious Pulmonary Adverse Events occurring within 7 days after each study PC transfusion

Mortality within 7 days after the last study PC transfusion, or until hospital discharge/discontinuation of outpatient platelet transfusion support, whichever is sooner (all deaths and deaths due to ARDS).

Cerus Corporation

Symptoms and General Pathology

Neoplasms

Recurrence

Glioblastoma

Glioma

Gliosarcoma

Disease Attributes

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

Gamma-retroviral MSGV1 139 scFv EGFRvIII CAR gene-modified T cells

EGFRvIII-CARs

Daniel Landi, MD

David Ashley, MBBS, FRACP, PhD

The goal of this protocol is to transfer autologous peripheral blood mononuclear cells (PBMCs) transduced with genes encoding a chimeric antigen receptor (CAR) that recognizes epidermal growth factor receptor variant III (EGFRvIII) tumor-specific antigen into patients with recurrent glioblastoma (GBM) following stereotactic radiosurgery (SRS). The CAR used is targeted to a tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, which is expressed on a subset of patients. Normal PBMCs derived from patients with GBM are genetically engineered with a viral vector encoding the CAR and infused directly into the patient's tumor with the aim of mediating regression of their tumors. Despite our CAR being targeted to a tumor specific antigen, given the prior toxicity using CARs that were not targeted to tumor-specific antigens, the investigators elected to begin with very low doses of cells. Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial.

Patients with evidence of radiographic recurrence who expressed EGFRvIII on their original tumor diagnosis had autologous PBMCs harvested by leukapheresis. These autologous PBMCs were transduced with a retrovirus containing the sequences for the EGFRvIII CAR and sent to the Duke Radiopharmacy for radiolabeling with 111Indium (111In). Within 2-3 weeks of leukapheresis, on Day -4 to -2, patients had a BrainLab MRI to prepare for biopsy and catheter placement. On Day -1, the patient underwent standard of care (SOC) stereotactic biopsy under local anesthesia to confirm tumor recurrence. At the time of biopsy, prior to catheter insertion and administration of study drug, the presence of recurrent tumor was confirmed by histopathology. If tumor recurrence was confirmed, a catheter was placed intratumorally for delivery of EGFRvIII-CARs by Convection Enhanced Delivery (CED).

SRS will took place on Day 0 (+1 day) and 111In-labeled EGFRvIII-CARs were infused on the same day over a 6 to 6.5 hour period immediately after SRS.

On days 1 and 2 after 111In-labeled EGFRvIII-CAR infusion, whole planar imaging followed by Single-Photon Emission Computed Tomography (SPECT) Computed Tomography (CT) imaging assessed the intracerebral and systemic localization of the 111In-labeled EGFRvIII-CARs that described the distribution of EGFRvIII-CARs within the brain and systemically.

This protocol was designed to determine the maximum tolerated dose (MTD) of a novel, tumor-specific treatment with autologous EGFRvIII-CARs. The proposed starting dose was 2.5 x 10\^8 of 111In-labeled cells in 3 milliliters (mL). The infusion flow rate was fixed at 0.5 mL/hr.

Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. Upon approval of this amendment, the enrollment suspension remained due to a change in access to necessary equipment for CAR manufacturing. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial. The knowledge gained from this study experience is directing our next CAR T-cell platform and will be used to secure additional funding.

Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM

INTERCEPT: INTracerebral EGFR-vIII Chimeric Antigen Receptor Gene-Modified T CElls for PaTients With Recurrent GBM

MTD of EGFRvIII-CAR gene-modified T cells when administered intracerebrally by CED after SRS in patients with recurrent GBM

Change in volume of distribution and maximal percentage of enhanced tumor volume covered

Change in the volume of distribution of 111In-labeled EGFRvIII-CARs present in each body area (neck, chest, abdomen, pelvis, and extremities)

The time between SRS / CAR treatment and death or last follow-up

The time between SRS / CAR treatment and first failure (death or disease progression)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Open Label, Post Marketing Surveillance Study Following Transfusion of INTERCEPT Platelet Components	NCT02549222	Transfusion Rel...	Standard of Car...	-	Cerus Corporation
Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM	NCT03283631	Recurrent Gliob... Recurrent Glios...	EGFRvIII-CARs	18 Years -	Duke University

Spots Global Cancer Trial Database for intercept

Every month we try and update this database with for intercept cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for intercept

Every month we try and update this database with for intercept cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for intercept cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.