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    The EU Clinical Trials Register currently displays   36119   clinical trials with a EudraCT protocol, of which   5940   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-000440-18
    Sponsor's Protocol Code Number:CD-TCR-001
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-07-12
    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 ConcernedGermany - PEI
    A.2EudraCT number2017-000440-18
    A.3Full title of the trial
    A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial with Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects with High Risk Myeloid and Lymphoid Neoplasms
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical dose-finding study to assess the safety and efficacy of gene-modified T cells in patients with high risk blood tumors
    A.3.2Name or abbreviated title of the trial where available
    A Phase I/II clinical trial for TCR modified T cells, MDG1011, in HR myeloid and lymphatic neoplasms
    A.4.1Sponsor's protocol code numberCD-TCR-001
    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 SponsorMedigene AG
    B.1.3.4CountryGermany
    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 supportMedigene AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedigene AG
    B.5.2Functional name of contact pointJessica Cordes
    B.5.3 Address:
    B.5.3.1Street AddressLochhamer Straße 11
    B.5.3.2Town/ cityPlanegg / Martinsried
    B.5.3.3Post code82152
    B.5.3.4CountryGermany
    B.5.4Telephone number+49892000330
    B.5.5Fax number+49892000332920
    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.3.2Product code MDG1011
    D.3.4Pharmaceutical form Dispersion for 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.3.8INN - Proposed INN11 Structurally Diverse Substance – Cell therapy
    D.3.9.2Current sponsor codeMDG1011
    D.3.9.3Other descriptive namePRAME-T-CELL RECEPTOR GENE MODIFIED AUTOLOGOUS T CELLS
    D.3.9.4EV Substance CodeSUB191003
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1x10E5 Tcell/kg to 1x10E7 Tcell/kg
    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 No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    High Risk Myeloid and Lymphoid Neoplasms
    E.1.1.1Medical condition in easily understood language
    High risk blood tumors (white blood cell cancer)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10061240
    E.1.2Term Malignant lymphoid neoplasm
    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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10000886
    E.1.2Term Acute myeloid leukemia
    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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    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 HLT
    E.1.2Classification code 10028536
    E.1.2Term Myelodysplastic syndromes
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level HLT
    E.1.2Classification code 10028229
    E.1.2Term Multiple myelomas
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028557
    E.1.2Term Myeloid leukemia, acute
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    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
    Phase I part:
    • To assess the safety and tolerability of MDG1011
    • To establish the maximum tolerated dose (MTD) and/or recommended Phase II dose (RPD2) of MDG1011
    • For feasibility, assess the percent of all subjects who receive the planned target dose of MDG1011

    Phase II part:
    Primary:
    • To further assess the safety and tolerability of MDG1011
    • To evaluate overall response rate (ORR)
    E.2.2Secondary objectives of the trial
    Phase I part:
    • To evaluate overall response rate (ORR)
    • To evaluate duration of response (DoR)
    • To evaluate time to progression (TTP)
    • To evaluate progression-free survival (PFS)
    • To assess overall survival (OS)
    • To evaluate quality of life (QoL)
    • To evaluate the correlation of PRAME expression with the antitumor response

    Phase II part:
    • To evaluate duration of response (DoR)
    • To evaluate time to progression (TTP)
    • To evaluate progression-free survival (PFS)
    • To assess overall survival (OS)
    • To evaluate quality of life (QoL)
    • For feasibility, assess the percent of all subjects who receive the RP2D of MDG1011
    • To evaluate the correlation of PRAME expression with the antitumor response
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Key inclusion criteria include:
    1. Signed written informed consent prior to any clinical trial related activities
    2. Documented diagnosis with the last disease staging within the last 4 weeks prior to screening
    3. Human leukocyte antigen (HLA)
    a. Phase I and Phase II (treatment group): Subjects positive for HLA-A*02:01 according to genotyping results
    b. Phase II (concurrent control group): Subjects negative for HLA-A*02:01 according to genotyping results
    4. Age ≥ 18 years
    5. Life expectancy of at least 4 months.
    6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
    7. Subjects not planned for allogeneic hematopoetic stem cell transplantation (HSCT) (e.g. based on disease characteristics or subject characteristics). Bridging to an allogeneic HSCT will be allowed.
    8. Negative pregnancy test in women of childbearing potential (before leukapheresis and before administration of lymphodepleting chemotherapy).
    9. For fertile men and women, agreement to use effective contraceptive methods during the clinical trial.

    Acute Myeloid Leukemia (AML)-specific inclusion criteria:
    1. No complete remission response (CR) or no complete remission with incomplete heamatologic recovery (CRi) after completion of at least 2 cycles of intensive induction chemotherapy or 1 cycle of intensive induction and consolidation (intermediate or high dose cytarabine chemotherapy),
    and/or
    2. No CR or no CRi after completion of at least 1 cycle of intensive induction chemotherapy including at least 5 days of cytarabine 100-200 mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 500 mg/m² per cycle and at least 2 days of an anthracycline (e.g. daunorubicin, idarubicin), unable to undergo allogeneic HSCT
    and/or
    3. Refractory disease (including stable disease [SD], progressive disease [PD]) or relapsed disease after hypomethylating agent therapy (e.g. azacitidine, decitabine),
    and/or
    4. Any SD, partial reponse (PR), CRi, CR obtained after re-induction or salvage therapy,
    and/or
    5. Relapsed AML patients unable to undergo allogeneic HSCT,
    and/or
    6. Relapsed AML after allogeneic HSCT;
    a. at least 100 days after transplant.
    b. no evidence of active acute or chronic GvHD at enrolment, in case of history of acute (> overall grade 1) or chronic GvHD (moderate/severe) requiring immunosuppressive treatment no immunosuppression within the last 3 months,
    c. no immunosuppression (with the exception of low-dose steroids ≤10 mg prednisone or equivalent) 4 weeks before enrollment and ongoing,
    and
    7. Myeloid blasts must positively express PRAME


    Myelodysplastic Syndrome (MDS)-specific inclusion criteria:
    1. International Prognostic Scoring System Intermediate-2 (IPSS INT-2) or High Grade MDS EB-2, not responding to at least 6 courses of azacitidine or 4 courses of decitabine and/or
    2. IPSS INT-1, INT-2 or High Grade MDS with recurrence after initial response and
    3. Blasts must positively express PRAME

    Multiple Myeloma-specific inclusion criteria:
    1. Relapsed and refractory multiple myeloma (MM)
    • Progressive MM, also defined as relapsed disease, defined as:
    a) A 25% increase from baseline in the serum M-protein (absolute increase ≥ 0.5 g/dL), urine M-protein (absolute increase > 200 mg/day), and/or the difference between involved and uninvolved free light chain levels (absolute increase ≥ 10 mg/dL).
    b) The presence of definite new bone lesions and/or soft tissue plasmacytomas with a clear increase in the size of existing plasmacytomas, or hypercalcemia, that cannot be attributed to another cause.
    • Relapsed and refractory MM is defined as disease progression within 60 days of a patient’s last treatment where at least a minimal response was achieved.
    • Primary refractory MM is defined as disease that fails to achieve at least a minimal response with any therapy.
    2. At least 3 previous therapy lines with at least one proteasome inhibitor and one immunomodulatory derivate (IMiDs). Induction with or without HSCT and with or without maintenance therapy is considered a single regimen.
    3. Myeloma cells must positively express PRAME

    Criteria for pre-emptive leukapheresis procedure:
    • subject is positive for HLA-A*02:01 and their blasts/myeloma cells express PRAME,
    • subject fulfills at least some inclusion criteria and, based on the judgement of the investigator, have a likelihood of being eligible for IMP administration in the further course of the subjects disease,
    • subject does not fulfill any exclusion criterion that would be considered permanent (i.e. irreversible organ function impairment) and therefore would certainly preclude the subject from receiving the IMP in the future.
    E.4Principal exclusion criteria
    Key exclusion criteria include:
    1. Subjects with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); Promyelocytic Leukemia/Retinoic Acid Receptor Alpha (PML-RARA), or with variant translocations
    2. Pregnant or lactating women
    3. Known positive for human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    4. Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the subjects at special risk, such as:
    a. Creatinine > 2.0 times the upper normal serum level
    b. total bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) > 3.0 times the upper normal serum level
    c. cardiac left ventricular ejection fraction < 40% at rest
    d. severe restrictive or obstructive lung disease
    5. History of haploidentical allogeneic stem cell transplantation
    6. Subjects both with urinary outflow obstructions and on dialysis or subjects for whom cyclophosphamide is contraindicated for other reasons
    7. Clinical significant and ongoing immune suppression including, but not limited to: immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of ≥10 mg prednisone per day). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed.
    8. Subjects with currently active autoimmune disease
    9. Subjects with a history of primary immunodeficiency
    10. Subjects with a currently active second malignancy other than non-melanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago
    11. Known or suspected hypersensitivity or intolerance to IMP, Cyclophosphamide, Fludarabine and/or tocilizumab or to any of the excipients
    12. Participation in any clinical trial < 60 days prior to first IMP administration in case of antibodies and < 14 days for all other IMPs
    13. Vulnerable subjects and/or subjects unwilling or unable to comply with procedures required in this clinical trial protocol

    MM-specific exclusion criteria for Phase I and Phase II (treatment group, in case MM proceeds to Phase II)
    1. Prior therapy with IMiDs within 14 days prior to leukapheresis and/or infusion of IMP
    2. Prior therapy with corticosteroids within 7 days prior to leukapheresis or 7 days prior to infusion of IMP

    Exclusion Criteria for treatment with IMP in Phase I and Phase II (treatment group):
    1. Uncontrolled central nervous system (CNS) disease
    2. Uncontrolled infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
    3. Ongoing ≥ 3 grade cardiac, renal, pulmonary, gastrointestinal or hepatic toxicities according to National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
    4. Evidence of acute or chronic GvHD

    Treatment Exemption Criterion:
    Unable to generate IMP for infusion; however, if a lower than planned number of cells is available (at least 1 x 105 T cells/kg), the subject in Phase I/II of the clinical trial will have the option to receive IMP and will be analyzed in the safety and full analysis set populations.
    E.5 End points
    E.5.1Primary end point(s)
    Phase I
    • Incidence and severity of adverse events ([AEs] at 3 months) according to the NCI CTCAE, v4.03
    • MTD and/or RP2D of IMP measured by dose-limiting toxicities (DLTs) up to 28 days post Infusion

    Phase II
    • Incidence and severity of adverse events ([AEs] at 3 months) according to NCI CTCAE, v4.03
    • Overall response rate (ORR) at 3 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Primary endpoint: Last Subject Last Visit 8 (month 3)
    E.5.2Secondary end point(s)
    Phase I
    • Incidence and severity of adverse events ([AEs] at 6 and 12 months) according to the NCI CTCAE, v4.03
    • Overall response rate (ORR) at 3, 6 and 12 months
    • Time to event and OS rate at 3, 6 and 12 months
    • Time to event and PFS rate at 3, 6 and 12 months
    • Time to event and DoR rate at 3, 6 and 12 months
    • Time to event and TTP rate at 3, 6 and 12 months
    • Percent of subjects undergoing HSCT after receiving IMP
    • Quality of Life (before infusion of IMP and after 3, 6, and 12 months)
    • Correlation of PRAME expression with the antitumor response

    Phase II
    • Incidence and severity of adverse events ([AEs] at 6 and 12 months) according to NCI CTCAE, v4.03
    • Overall response rate (ORR) at 6 and 12 months
    • Time to event and OS rate at 3, 6 and 12 months
    • Time to event and PFS rate at 3, 6 and 12 months
    • Time to event and DoR rate at 3, 6 and 12 months
    • Time to event and TTP rate at 3, 6 and 12 months
    • Percent (%) of subjects undergoing HSCT after receiving IMP
    • Quality of Life (before infusion of IMP and after 3, 6, and 12 months)
    • Correlation of PRAME expression with the antitumor response
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Secondary endpoint:
    Last Subject Last Visit 9 (month 6)
    Last Subject Last EoT Visit (month 12)
    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 Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Feasibility
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    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 Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3.1Comparator description
    The patient in the control group will receive therapy as per Investigator's discretion
    E.8.2.4Number of treatment arms in the trial2
    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 concerned11
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    • Primary endpoint: LSLV 8 (month 3)
    • Secondary endpoint:
    LSLV Visit 9 (month 6)
    LSLV EoT (month 12)
    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 months7
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 52
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state92
    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)
    Subjects will be followed up in a separate long-term follow-up clinical trial, for which they can be enrolled upon leaving this clinical trial. Long-term follow-up is defined as an additional 14 years.
    Subjects will no longer receive IMP MDG1011 but will be allowed to receive any treatment chosen by their treating physician.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-12-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-20
    P. End of Trial
    P.End of Trial StatusOngoing
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