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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04044768
Other study ID # ADP 0044-002
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 13, 2019
Est. completion date April 1, 2038

Study information

Verified date February 2024
Source Adaptimmune
Contact Adaptimmune Patient Enquiries
Phone 215-825-9260
Email patients@adaptimmune.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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) .


Recruitment information / eligibility

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.

Study Design


Intervention

Genetic:
afamitresgene autoleucel (previously ADP-A2M4)
Single infusion of autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) Dose: 1.0 x109 to 10x109 transduced by a single intravenous infusion

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain,  United Kingdom, 

Outcome

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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