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    Summary
    EudraCT Number:2015-005594-21
    Sponsor's Protocol Code Number:ADP-04511
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-06-08
    Trial results View 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 number2015-005594-21
    A.3Full title of the trial
    A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1c259T in HLA-A2+ Patients with Synovial Sarcoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Pilot Study of NY-ESO-1c259T in Synovial Sarcoma
    A.3.2Name or abbreviated title of the trial where available
    A Pilot Study of NY-ESO-1c259T in Synovial Sarcoma
    A.4.1Sponsor's protocol code numberADP-04511
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01343043
    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 support
    B.4.2Country
    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 code19112
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 (215) 825 9260
    B.5.5Fax number+1 (215) 405 3956
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1694
    D.3 Description of the IMP
    D.3.1Product nameNY-ESO-1c259T
    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 codeNY-ESO-1c259T
    D.3.9.3Other descriptive nameNY-ESO-1c259 SPEAR T-cells
    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 Yes
    D.3.11.8Extractive medicinal product Yes
    D.3.11.9Recombinant medicinal product Yes
    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
    Unresectable, metastatic or recurrent synovial sarcomas
    E.1.1.1Medical condition in easily understood language
    Advanced synovial sarcoma (Soft tissue tumours)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10042863
    E.1.2Term Synovial 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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • Determine the response rate in patients with unresectable, metastatic or recurrent synovial sarcoma treated with lymphodepletion and Treg depletion followed by adoptive immunotherapy with T cells engineered to recognize an HLA-A2 restricted NY-ESO-1 derived peptide (Cohort 1)

    • Determine the response rate and duration of response of adoptive immunotherapy with NY ESO 1c259T cells in patients with synovial sarcoma and low-level expression of NY ESO 1 (Cohort 2)

    • Determine the response rate and duration of response of adoptive immunotherapy with NY ESO 1c259T cells in patients with synovial sarcoma treated with a lymphodepleting regimen containing cyclophosphamide as a single cytotoxic agent (Cohort 3)

    • Determine the response rate and duration of response of adoptive immunotherapy with NY ESO 1c259T cells in patients with synovial sarcoma treated with a lymphodepleting regimen containing cyclophosphamide and fludarabine cytotoxic agents at reduced total doses (Cohort 4)
    E.2.2Secondary objectives of the trial
    • Determine the safety of treatment with adoptively transferred NY-ESO-1c259T.
    • When possible, assess whether patients with progressive disease following NY-ESO-1c259T T-cell infusion or who do not respond (Cohorts 3 and 4) experience a response following a second dose
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Pathologically or histologically confirmed synovial sarcoma that has been treated with a standard chemotherapy regimen containing ifosfamide and/or doxorubicin, is intolerant of or not actively responding to this regimen and remains:
    • unresectable or (intent is not to enrol patients with resectable tumors)
    • metastatic or progressive/persistent or recurrent
    2. Patients must have measurable disease in order to allow assessment of an anti-tumor response
    3. Pathologic review by a central laboratory designated by the Sponsor and confirming NY-ESO-1 expression by immunohistochemistry (IHC). Patients must have proven positive tumor sample for NY-ESO-1 as follows:
    Cohort 1: Positive expression is defined as 2+ or 3+ by IHC in ≥ 50% cells
    Cohort 2: Positive expression is defined as ≥ 1+ by IHC in ≥ 1% cells but not to exceed 2+ or 3+ in ≥ 50% cells
    Cohort 3: Positive expression is defined as 2+ or 3+ by IHC in ≥ 50% cells
    Cohort 4: Positive expression is defined as 2+ or 3+ by IHC in ≥ 50% cells
    4. HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 by high resolution testing
    5. Patient is ≥4 years of age on the day the Informed Consent is signed
    6. Patients must be >18 kg, for apheresis safety purposes
    7. Patients may have received salvage chemotherapy or other therapies. Prior Therapies
    All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy should be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepleting chemotherapy
    Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepleting chemotherapy
    Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepleting chemotherapy
    Any grade 3 or 4 hematologic toxicity of previous therapy must have resolved to grade 2 or less (or to values specified below) prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less (or to values specified below) prior to pre-infusion lymphodepleting chemotherapy
    8. Performance status: ECOG 0-1, or for children ≤10 years of age, Lansky >60
    9. Life expectancy >3 months
    10. Patient must have adequate organ function as indicated by the following laboratory values below
    Absolute Neutrophil count (ANC) ≥ 1.0 x10^9/L
    Platelets ≥ 75 x10^9/L (not achieved by transfusion)
    Creatinine clearance ≥ 40 ml/min
    Patients <65 yrs of age can be assessed using estimated creatinine clearance calculated using the Cockcroft and Gault formula
    Patients ≥65 yrs of age must have renal function measured either by 24-hour urine creatinine collection or by nuclear medicine GFR measurement, according to standard practice at the treating institution
    Serum total bilirubin < 2 mg/dl
    (If patient has Gilberts syndrome: total bilirubin <3xULN and direct bilirubin <35%)
    Serum AST and ALT ≤ 2.5 x Upper Limit of Normal
    Left ventricular ejection fraction ≥40%, or Fractional Shortening ≥28%
    11. Ability to give informed consent prior to any study-specific procedures. Any standard of care procedures (e.g., lab tests, scans) can be used for purposes of assessing study eligibility as long as all other requirements as stated in the protocol are met. For patients <18 years of age (or the legal minimum age in the relevant country) their legal guardian must give informed consent. Pediatric patients will be included in age-appropriate discussion in order to obtain verbal assent
    12. Female patients of childbearing potential (FCBP) must have a negative urine or serum pregnancy test. NOTE: FCBP is defined as not surgically sterilized and premenopausal
    FCBP must agree to use an effective method of contraception, starting at the first dose of chemotherapy for at least 12 months thereafter and 4 months after the gene modified cells are no longer detected in the blood due to the known expression of the target antigen on fetal germ line tissues and placenta
    Effective methods of contraception include: intra-uterine device, injectable hormonal contraception, oral contraception, or 2 adequate barrier methods (e.g. diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide - spermicides alone are not an adequate method of contraception)
    Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle
    13. Male patients must be willing to practice birth control starting at the first dose of chemotherapy and for 4 months thereafter or longer (if indicated in the country specific monograph/label for cyclophosphamide). Effective methods of contraception are detailed in Inclusion criterion #12
    E.4Principal exclusion criteria
    1. Clinically significant systemic illness (e.g. serious active infections or significant cardiac,
    pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications
    2. Untreated CNS metastasis. Extradural masses that have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible. Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks are eligible.
    3. Previous treatment with genetically engineered NY-ESO-1 specific T cells.
    4. Pregnant or breastfeeding females (due to risk to fetus or newborn).
    5. Active HIV, HBV, HCV or HTLV 1 or 2 infection as defined below (due to increased risk of complications during the lymphodepleting regimen and confounding effects on the immune system):
    • 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 subjects as demonstrated by test for hepatitis C RNA. Subjects who are HCV antibody positive will be screened for HCV RNA by any RT PCR or bDNA assay. Eligibility will be determined based on a negative screening value.
    • Positive serology for HTLV 1 or 2.
    6. Subject has history of active, chronic or recurrent (within the last year prior to enrolment) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
    E.5 End points
    E.5.1Primary end point(s)
    (1) Determine the response rate in patients with unresectable, metastatic or recurrent synovial sarcoma treated with lymphodepletion and Treg depletion followed by adoptive immunotherapy with T cells engineered to recognize an HLA-A2 restricted NY-ESO-1 derived peptide (Cohort 1).

    (2)Determine the response rate and duration of response of adoptive immunotherapy with NY-ESO-1c259T cells in patients with synovial sarcoma and low-level expression of NY-ESO-1 (Cohort 2).

    (3)Determine the response rate and duration of response of adoptive immunotherapy with NY-ESO-1c259T cells in patients with synovial sarcoma patients treated with a lymphodepleting regimen containing cyclophosphamide as a single cytotoxic agent (Cohort 3).

    (4) Determine the response rate and duration of response of adoptive immunotherapy with NY-ESO-1c259T cells in patients with synovial sarcoma treated with a lymphodepleting regimen containing cyclophosphamide and fludarabine cytotoxic agents at reduced total doses (Cohort 4).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Response is evaluated post infusion of NY-ESO-1c259T at 4, 8, 12 weeks, 6, 9 and 12 months, then every 3 months until 2 years, then every 6 months until 5 years post infusion, until progression or discontinuation.
    E.5.2Secondary end point(s)
    (1) Determine the safety of treatment with adoptively transferred NY-ESO-1c259T.
    (2) When possible, assess whether patients with progressive disease following NY-ESO-1c259T or who do not respond (Cohorts 3 and 4) experience a response following a second dose.
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA1
    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
    United States
    E.8.7Trial has a data monitoring committee No
    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
    Last visit of the last subject undergoing the trial.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 2
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 1
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 1
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 Information not present in EudraCT
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 3
    F.4.2.2In the whole clinical trial 60
    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)
    NY-ESO-1c259T (T-cell infusion) will be given as a one time treatment, with potential for a second infusion under some circumstances. As a result provision for continued treatment is not applicable.
    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 Decision2016-08-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-08-18
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2019-06-18
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    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
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