Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-000589-39
    Sponsor's Protocol Code Number:ADP-0044-002
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-08-06
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2019-000589-39
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to assess the safety and efficacy of T cell therapy in patients with advanced cancer
    A.3.2Name or abbreviated title of the trial where available
    A phase 2 single arm, open phase study of ADP-A2M4 SPEAR T cells
    A.4.1Sponsor's protocol code numberADP-0044-002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04044768
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAdaptimmune LLC
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAdaptimmune LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAdaptimmune LLC
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address351 Rouse Blvd
    B.5.3.2Town/ cityPhiladelphia
    B.5.3.3Post codePA 19112
    B.5.3.4CountryUnited States
    B.5.4Telephone number2158259328
    B.5.6E-mailRegAffairs@adaptimmune.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameADP-A2M4
    D.3.2Product code ADP-A2M4
    D.3.4Pharmaceutical form Infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeADP-A2M4
    D.3.9.4EV Substance CodeAS1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Synovial sarcoma, Myxoid round cell liposarcoma
    E.1.1.1Medical condition in easily understood language
    Soft tissue cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10075333
    E.1.2Term Soft tissue sarcoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10075333
    E.1.2Term Soft tissue sarcoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of autologous
    genetically modified T cells (ADP-A2M4) in HLA-A*02 positive patients with
    MAGE-A4 expressing advanced synovial sarcoma or MRCLS .
    E.2.2Secondary objectives of the trial
    Study secondary objectives are:
    - To evaluate the safety and tolerability of
    autologous genetically modified T cells (ADP-A2M4) in HLA-A*02 positive patients with MAGE-A4 expressing advanced
    synovial sarcoma or MRCLS
    - To evaluate the efficacy of autologous genetically modified T cells (ADP-A2M4)
    in HLA-A*02 positive patients with MAGE-A4 expressing advanced synovial sarcoma or MRCLS
    - Development and validation of an in vitro diagnostic (IVD) assay for the screening of tumor antigen expression for
    regulatory approval
    - Characterise the in vivo cellular pharmacokinetics (PK) profile of ADPA2M4 cells
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject (or legally authorized representative) voluntarily agrees to participate by giving written Informed Consent
    (and Assent as applicable)in accordance with ICH GCP guidelines and applicable local regulations.
    2. Subject (or legally authorized representative) agrees to abide by all protocol required procedures including study
    related assessments and management by the treating institution for the duration of the study, including long term
    follow-up.
    3. Age ≥16 and <75 years at the time the Pre-screening informed consent/assent is signed.
    4. Diagnosis of advanced (metastatic or inoperable) synovial sarcoma or myxoid liposarcoma / myxoid round cell
    liposarcoma confirmed by cytogenetics. Inoperable refers to a tumor lesion in which clear surgical excision margins
    cannot be obtained without leading to significant functional compromise.
    a. For Synovial Sarcoma: confirmation by the presence of a translocation between SYT on the X chromosome and
    SSX1, SSX2 or, SSX4 on chromosome 18 (may be presented in the pathology report as t (X; 18)).
    b. For MRCLS: confirmation by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11) or t(12; 22)
    (q13;q12)
    5. Must have previously received either an anthracycline or ifosfamide containing regimen. Subjects who are intolerant
    to both anthracycline and ifosfamide must have previously received at least one systemic therapy.
    6. Measurable disease according to RECIST v1.1.
    7. Positive for HLA-A*02:01, HLA-A*02:03, HLA-A*02:06 allele via Adaptimmune designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as these alleles in the peptide binding domains (P group) will also be included. Other HLA-A*02 alleles may be eligible after adjudication with the sponsor.
    8. Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of ≥2+ staining in ≥30% of the
    cells by immunohistochemistry. All samples must have been pathologically reviewed by an Adaptimmune designated
    central laboratory confirming expression.
    9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
    10. Left ventricular ejection fraction (LVEF) ≥50%.
    11. Fit for leukapheresis and adequate venous access can be established for the
    cell collection.
    12. Female subjects of childbearing potential (FCBP) must have a negative urine or serum pregnancy test AND mustagree to use an effective method of contraception starting at the first dose of chemotherapy and continuing for at least
    12 months, or 4 months after the gene modified cells are no longer detected in the blood, whichever is longer.
    − OR
    Male subjects must be surgically sterile or agree to use a double barrier contraception method or abstain from
    heterosexual activity with a FCBP starting at the first dose of chemotherapy and continuing for 4 months thereafter (or
    longer if indicated in the country specific monograph/label for cyclophosphamide).
    13. Must have adequate organ function as indicated by the laboratory values in
    a table from the protocol. Please see protocol page 20
    E.4Principal exclusion criteria
    1. Positive for HLA-A*02:05 in either allele via Adaptimmune designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as HLA-A*02:05 in the peptide binding domain (P groups) will also be excluded. Other alleles may be exclusionary after adjudication with the sponsor.
    2. Received or plans to receive therapy/treatment prior to leukaphereseisis or lymphodepleting chemotherapy
    3. Toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment (except for nonclinically
    significant toxicities, e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or
    irreversible (e.g. peripheral neuropathy) can be enrolled.
    4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine,
    cyclophosphamide or other agents used in the study.
    5. History of autoimmune or immune mediated disease. Subjects with hypothyroidism, diabetes, adrenal insufficiency
    or pituitary insufficiency that are stable on replacement therapy are eligible. Subjects with disorders such as asthma,
    psoriasis or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also
    eligible.
    6. Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases. Subjects with a prior
    history of symptomatic CNS metastases must have received treatment (i.e., stereotactic radiosurgery (SRS), whole
    brain radiation (WBRT) or surgery) and be neurologically stable for at least 1 month, not requiring anti-seizure
    medications and off of steroids for at least 14 days prior to leukapheresis and lymphodepletion. Antiseizure
    prophylaxis is permitted. Subjects who have
    asymptomatic CNS metastases without associated edema, shift, requirement for steroids
    or anti-seizure medications for the treatment of seizures are eligible.
    7. Any other prior malignancy that is not in complete remission. Resectable
    squamous or basal cell carcinoma of the skin is acceptable. Prior malignancies that have been surgically resected
    and show no evidence of disease are acceptable.
    8. Uncontrolled intercurrent illness including, but not limited to:
    Ongoing or active infection;
    • Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class 3
    or Class 4;
    • Uncontrolled clinically significant arrhythmia;
    Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months;
    • Interstitial lung disease (subjects with existing pneumonitis as a result of radiation are not excluded, however,
    subjects must not be oxygen dependent);
    • Congenital or family history of long QT syndrome;
    • Current uncontrolled hypertension despite optimal medical therapy;
    • History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic
    neurologic deficit (RIND) in last 6 months;
    9. Active infection with HIV, HBV, HCV or HTLV as defined below:
    • Positive serology for HIV;
    • Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B
    surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and
    receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and
    continued for 6 months;
    Active hepatitis C infection as demonstrated by hepatitis C RNA test. Subjects who are HCV antibody positive will be
    screened for HCV RNA by any RT PCR or bDNA assay. If HCV antibody is positive, eligibility will be determined based
    on a negative screening RNA value;
    • Positive serology for HTLV 1 or 2;
    • Re-screening for infectious disease markers is not required at baseline
    (prior to lymphodepletion) unless > 6 months has elapsed.
    10. Pregnant or breastfeeding.
    11. In the opinion of the Investigator, the subject is unlikely to fully comply
    with protocol requirements.
    E.5 End points
    E.5.1Primary end point(s)
    Overall Response Rate (ORR) per RECIST v1.1 by independent review
    E.5.1.1Timepoint(s) of evaluation of this end point
    Anytime during the study
    E.5.2Secondary end point(s)
    Safety and tolerability
    • Adverse events (AEs) including serious adverse events (SAEs)
    • Incidence, severity and duration of the AEs of special interest
    • Replication Competent Lentivirus (RCL)
    • T cell Clonality and Insertional oncogenesis (IO).
    Efficacy
    • Time to Response (TTR)
    • Duration of Response (DoR)
    • Best Overall Response (BOR)
    • Progression Free Survival (PFS)
    • Overall Survival (OS).
    Development and validation of an in vitro diagnostic (IVD) assay
    • Retention of additional tumor tissue during Pre-screening to enable development and validation of the MAGE-A4
    antigen expression companion diagnostic assay
    PK
    •Peak persistence and other relevant PK parameters of ADP-A2M4 cells
    E.5.2.1Timepoint(s) of evaluation of this end point
    Anytime during the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    France
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days11
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days27
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 27
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 13
    F.4.2.2In the whole clinical trial 45
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Upon completion of the study, patients will be managed under standard of care.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-10-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-05
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 10:16:18 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA