Synovial Sarcoma Clinical Trial
Official title:
A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .
Status | Recruiting |
Enrollment | 120 |
Est. completion date | April 1, 2038 |
Est. primary completion date | October 10, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 10 Years to 75 Years |
Eligibility | Key Inclusion Criteria - Age =16 (10 years at selected sites) and <=75 years - Diagnosis of advanced synovial sarcoma (Cohort 1, Cohort 2 and Cohort 3) or myxoid liposarcoma / myxoid round cell liposarcoma (Cohort 1 only) confirmed by cytogenetics. - Previously received either an anthracycline or ifosfamide containing regimen. - Measurable disease according to RECIST v1.1 prior to lymphodepletion - HLA-A*02:01, HLA-A*02:02, HLA-A*02:03 or HLA-A*02:06 positive - Tumor shows MAGE-A4 expression confirmed by central laboratory. North America Only (United States and Canada): Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of =1+ staining in =10% of the cells by immunohistochemistry. - ECOG Performance Status of 0 or1. For subjects aged =10 to =16 years old: Lansky Score =60%. • Left ventricular ejection fraction (LVEF) =50%. Note: other protocol defined Inclusion criteria may apply Key Exclusion Criteria: - HLA-A*02:05 in either allele - Received or plans to receive the following therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy, Tyrosine kinase inhibitor (TKI) (e.g. pazopanib), Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors,), Anti-cancer Vaccine, Gene therapy using an integrating vector (subjects who have received a gene therapy using a lentiviral vector may be eligible for the study), Corticosteroids or any other immunosuppressive therapy, Investigational treatment or interventional clinical trial, Allogeneic hematopoietic stem cell transplant, Radiotherapy to the target lesions, Major surgery - History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. - History of autoimmune or immune mediated disease - Symptomatic CNS metastases including leptomeningeal disease. - Other prior malignancy that is not considered by the Investigator to be in complete remission - Clinically significant cardiovascular disease - Uncontrolled intercurrent illness - Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus - Pregnant or breastfeeding Note: other protocol defined Exclusion criteria may apply. |
Country | Name | City | State |
---|---|---|---|
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
France | Centre Leon Berard | Lyon | |
France | Hospital Haut Leveque, CHU Bordeaux | Pessac | |
France | Gustave Roussy Cancer Center | Villejuif | |
Spain | Hospital Universitari Vall D'Hebron | Barcelona | Cataluna |
Spain | Start Madrid-FJD, Fundación Jim?nez Díaz | Madrid | |
Spain | Hospital Universitario Virgen del Rocio | Sevilla | |
United Kingdom | UCLH Cancer Clinical Trials Unit | London | |
United Kingdom | The Christie NHS Foundation Trust | Manchester | |
United States | University of Michigan | Ann Arbor | Michigan |
United States | University of Colorado | Aurora | Colorado |
United States | National Cancer Institute | Bethesda | Maryland |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | Northwestern University Robert H. Lurie Comprehensive Cancer Center | Chicago | Illinois |
United States | Ohio State University | Columbus | Ohio |
United States | City of Hope | Duarte | California |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Mayo Clinic Jacksonville | Jacksonville | Florida |
United States | Medical College of WI Froedtert Hospital | Milwaukee | Wisconsin |
United States | Vanderbilt | Nashville | Tennessee |
United States | Columbia University | New York | New York |
United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
United States | Stanford Cancer Center | Palo Alto | California |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Fred Hutch | Seattle | Washington |
United States | Moffitt Cancer Center | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Adaptimmune |
United States, Canada, France, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Efficacy: Overall Response Rate (ORR) | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 | 2.5 years | |
Secondary | Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs) | 2.5 years | |
Secondary | Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells | Evaluation of RCL using PCR -based assay in peripheral blood. | 15 years | |
Secondary | Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs). | Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs ) | 2.5 years | |
Secondary | Efficacy: Best overall response (BOR) | BOR is per RECIST V1.1. | 2.5 years | |
Secondary | Time to response (TTR) | For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed. | 2.5 years | |
Secondary | Duration of Response (DoR) | For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death. | 2.5 years | |
Secondary | Progression Free Survival (PFS) | PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death. | 2.5 years | |
Secondary | Overall Survival (OS) | OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death | 15 years | |
Secondary | Quantitation of genetically engineered T-cells in PBMCs | Quantitation of genetically engineered T-cells in PBMCs by qPCR | 2.5 years | |
Secondary | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry | 2.5 years | |
Secondary | Quantitation of genetically engineered T-cells in PBMCs | Quantitation of genetically engineered T-cells in PBMCs by flow cytometry | 2.5 years | |
Secondary | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR | 2.5 years | |
Secondary | In vitro diagnostic (IVD) assay for screening | Development and validation of the MAGE-A4 antigen expression companion diagnostic assay | 2.5 years |
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