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   43917   clinical trials with a EudraCT protocol, of which   7306   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:2020-003908-14
    Sponsor's Protocol Code Number:M-2020-371
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-04-29
    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 number2020-003908-14
    A.3Full title of the trial
    A pivotal Phase II randomised, multi-centre, open-label study to evaluate the efficacy and safety of MB-CART2019.1 compared to standard of care therapy in participants with relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL), who are not eligible for high-dose chemotherapy and autologous stem cell transplantation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate efficacy and safety of MB-CART2019.1 compared with usual medication for patients with diffuse large B-cell lymphoma
    A.3.2Name or abbreviated title of the trial where available
    DALY 2-EU
    A.4.1Sponsor's protocol code numberM-2020-371
    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 SponsorMiltenyi Biomedicine GmbH
    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 supportMiltenyi Biomedicine GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMiltenyi Biomedicine GmbH
    B.5.2Functional name of contact pointDirector Clinical Development
    B.5.3 Address:
    B.5.3.1Street AddressFriedrich-Ebert-Straße 68
    B.5.3.2Town/ cityBergisch Gladbach
    B.5.3.3Post code51429
    B.5.3.4CountryGermany
    B.5.4Telephone number+49220483066694
    B.5.5Fax number+49220483066699
    B.5.6E-mailsilke.holtkamp@miltenyi.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/3/20/2327
    D.3 Description of the IMP
    D.3.1Product nameMB-CART2019.1
    D.3.4Pharmaceutical form Solution 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 INNZamtocabtagene autoleucel
    D.3.9.2Current sponsor codeMB-CART2019.1
    D.3.9.3Other descriptive nameAUTOLOGOUS T CELLS TRANSDUCED WITH LENTIVIRAL VECTOR CONTAINING A TANDEM CHIMERIC ANTIGEN RECEPTOR DIRECTED AGAINST CD20 AND CD19
    D.3.9.4EV Substance CodeSUB202852
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number2.5
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name GEMCITABINA HIKMA
    D.2.1.1.2Name of the Marketing Authorisation holderHikma Farmaceutica (Portugal), S.A.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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.3.4Pharmaceutical form Powder for solution 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 INNGEMCITABINE HYDROCHLORIDE
    D.3.9.1CAS number 95058-81-4
    D.3.9.4EV Substance CodeSUB02324MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Truxima 500 mg concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderCelltrion Healthcare Hungary Kft.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical form Concentrate for solution 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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal antibody
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Oxaliplatin 5mg/ml concentrate for Solution for Infusion
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameOxaliplatin
    D.3.4Pharmaceutical form Concentrate for solution 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 INNOXALIPLATIN
    D.3.9.1CAS number 61825-94-3
    D.3.9.4EV Substance CodeSUB09490MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    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.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Polivy 140 mg powder for concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namePolatuzumab vedotin
    D.3.4Pharmaceutical form Powder for concentrate for solution 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 INNPOLATUZUMAB VEDOTIN
    D.3.9.1CAS number 1313206-42-6
    D.3.9.4EV Substance CodeSUB177827
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal antibody
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Bendamustine hydrochloride Accord 2.5 mg/ ml Powder for concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare S.L.U.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameBendamustine hydrochloride
    D.3.4Pharmaceutical form Powder for concentrate for solution 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 INNBENDAMUSTINE HYDROCHLORIDE
    D.3.9.1CAS number 3543-75-7
    D.3.9.4EV Substance CodeSUB00696MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    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
    Relapsed/refractory diffuse large B cell lymphoma (R-R DLBCL)
    E.1.1.1Medical condition in easily understood language
    Diffuse large B cell lymphoma (DLBCL)
    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 10003903
    E.1.2Term B-cell lymphoma refractory
    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 PT
    E.1.2Classification code 10003902
    E.1.2Term B-cell lymphoma recurrent
    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 is to determine superiority of MB-CART2019.1 treatment compared to standard-of-care (SoC) therapy with R-GemOx (rituximab, gemcitabine and oxaliplatin) with respect to progression-free survival in second-line therapy in participants with R-R DLBCL, who are non-eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT).
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of MB-CART2019.1 compared to SoC therapy.
    • To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.
    • To evaluate changes in health-related quality of life (HRQoL) and lymphoma symptoms of participants receiving MB-CART2019.1 compared to SoC therapy.
    •To evaluate the humoral immunogenicity against MB-CART2019.1.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically proven DLBCL and associated subtypes, according to the World Health Organisation (WHO) 2016 classification including:
    • DLBCL not otherwise specified (NOS).
    • High grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements with DLBCL/blastoid/intermediate histology or HGBL with MYC and BCL2 and/or BCL6 rearrangements (double hit lymphoma/triple hit lymphoma).
    • High-grade BCL, NOS.
    • Primary (thymic) large mediastinal BCL.
    • Disease transformed from an earlier diagnosis of low-grade lymphoma (e.g. an indolent pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with DLBCL disease progression subsequent to DLBCL directed systemic treatment.
    • Follicular lymphoma Grade 3B.
    2. Relapsed or refractory disease after first-line chemoimmunotherapy:
    • Refractory disease is defined as no CR to first-line therapy(e.g. R-CHOP [rituximab, cyclophosphamide, daunorubicin, vincristine and prednisone]).
    - Progressive disease (PD) as best response after at least 2 full cycles of first-line therapy.
    - Stable disease (SD) after 4 cycles of first-line therapy.
    - PR as best response after at least 6 cycles of first-line therapy and biopsy-proven persistent disease (except where prohibited due to comorbidities) within ≤ 12 months from the completion of the first-line therapy.
    • Relapsed disease defined as complete remission to a first-line therapy followed by biopsy-proven disease progression (except where prohibited due to comorbidities) within ≤ 12 months from the completion of the first-line therapy.
    3. Participants must have received adequate first-line therapy containing at least the combination of an anthracycline-based regimen and rituximab (anti-CD20 monoclonal antibody). Local therapies (e.g. radiotherapies) will not be considered as line of therapy if performed during the same line of treatment.
    4. Archival paraffin-embedded tumour tissue acquired ≤ 2 years (preferred: ≤ 2 months) prior to screening for central pathology review to confirm DLBCL diagnosis must be made available for participation in this study. If archival paraffin-embedded tumour tissue is not available, fresh tumour tissue sample (preferred) or core-needle biopsy must be made available for the central pathology review.
    5. Participants deemed ineligible to receive HDC followed by ASCT based on the treating physician’s assessment and meeting the following criteria:
    EITHER
    • Age ≥ 18 years and
    - Prior ASCT (as first-line consolidation) or
    - Haematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) > 3.
    OR
    • Age ≥ 65 years and ≥ 1 of the criteria below:
    - Impaired cardiac function (left ventricular ejection fraction (LVEF) < 50%), or
    - Impaired renal function ((estimated glomerular filtration rate [eGFR] < 60 mL/min) calculated according to the modified Modification of Diet in Renal Disease (MDRD) formula, or
    - Impaired pulmonary function (diffusing capacity for carbon monoxide or forced expiratory volume in 1 second of < 80%) or dyspnoea on slight activity, or
    - Eastern Cooperative Oncology Group (ECOG) performance status > 1.
    OR
    • Age ≥ 70 years.
    Documentation of the reason for ineligibility for ASCT must be present in the participant’s source data.
    In addition, all participants must fulfil the following criteria:
    6. Age ≥ 18 years.
    7. Measurable disease according to Lugano criteria. The lesion must be measurable (nodes> 1.5 cm in the long axismeasurable (nodes > 1.5 cm in the long axis; extranodal lesions > 1 cm in the long axis) and positive on a positron emission tomography scan.
    8. Estimated life expectancy of > 3 months for other reasons than the primary disease.


    FOR FULL LIST OF INCLUSION CRITERIA PLEASE REFER TO THE STUDY PROTOCOL

    E.4Principal exclusion criteria
    1. Contraindications for R-GemOx,BR plus polatuzumab vedotin, cyclophosphamide and fludarabine as judged by the treating physician.
    2. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
    3. Participants who have received more than one line of treatment for DLBCL or associated subtypes.
    4. Prior haematopoietic stem cell transplantation (HSCT; as first-line consolidation) < 3 months at the time of leukapheresis.
    5. ECOG performance status > 2.
    6. Absolute lymphocyte count < 100/µL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow
    biopsy).
    7. Platelet count < 50,000/µL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow biopsy).
    8. Absolute lymphocyte count < 100/µL.
    9. Participants who have central nervous system (CNS) lymphoma involvement in present or past medical history.
    10. Participants with the requirement for urgent therapy due to tumour mass effects.
    11. Infection with human immunodeficiency virus.
    12. Presence of active or prior hepatitis B or C as indicated by serology (for detailed criteria see Section 10.2.7.10). Treated infection with
    hepatitis B or C virus unless confirmed to be polymerase chain reaction negative.
    13. Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
    14. Active, severe systemic fungal, viral or bacterial infection.
    15. Known history or evidence of severely immunocompromised state, i.e. corticosteroid treatment > 10 mg/day for more than 6 months.
    16. Has received vaccination with live virus vaccines 6 weeks prior to randomisation.
    17. Prior CD19-targeted therapy
    18. Known history or presence of seizure activities or on active antiseizure medications within the previous 12 months.
    19. History or presence of non-malignant CNS disease that, in the judgement of the investigator, may impair the ability to evaluate neurotoxicity.
    20. Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory
    disease.
    21. Known history or presence of cerebral vascular accident (CVA) within 12 months prior to randomisation. Note: In case of history of CVA
    > 12 months prior to leukapheresis, then the participant must not have any unstable or life-threatening neurological deficits.
    22. Participants with Richter's transformation or Richter's syndrome.
    23. Participants who are concurrently on any other experimental treatments or during the previous 4 weeks or 5-half-lives.
    24. Clinical heart failure with New York Heart Association class ≥ 2 or LVEF < 30% or severe cardiac arrhythmias or QT prolongation (resting
    QTcF ≥ 450 msec [male] or ≥ 460 msec [female] at screening) that would (according to the evaluation of the investigator) face an
    uncontrollable risk by receiving the medications administered in the trial.
    25. Resting peripheral oxygen saturation < 90% on room air.
    26. Liver dysfunction as indicated by total bilirubin > 2.5 × institutional upper limit of normal (ULN), aspartate aminotransferase and/or alanine
    aminotransferase > 5 × ULN or typical symptoms like jaundice.
    27. Serum creatinine ≥ 2.0 × ULN or eGFR < 30 mL/min calculated according to the modified MDRD formula.
    28. Pregnant or breast-feeding women.
    29. Prior history of malignancies other than DLBCL. Exceptions include participants who have been free of the disease for ≥ 3 years prior to
    screening and participants with adequately treated and removed basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
    carcinoma in situ of the cervix, carcinoma in situ of the breast, carcinoma in situ of the bladder or incidental histological finding of
    untreated localised (T1a, T1b and T1c) prostate cancer under surveillance.
    30. History of severe immediate hypersensitivity to any investigational medicinal product (IMP), auxiliary medicinal product (AMP),
    premedication or rescue medication or its excipients that is scheduled to be given during study participation.
    31. Major surgery less than 30 days before start of treatment.
    32. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival (PFS), defined as the time between the date of randomisation and the date of objective disease progression or death of any cause, whichever occurs first, based on Independent Review Committee (IRC) assessment.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The time between the date of randomisation and the date of objective disease progression or death of any cause, whichever occurs first, based on Independent Review Committee (IRC) assessment.
    E.5.2Secondary end point(s)
    Key Efficacy Endpoints:
    1. Event-free-survival (EFS), defined as the time between the date of randomisation and the date of the event (objective disease progression,
    the start of new anti-lymphoma therapy or death of any cause) based on IRC assessment.
    2. Best complete response rate (BCRR), defined as the proportion of participants with at least one complete response (CR) assessment until
    Week 24 in the MB-CART2019.1 arm and Week 26 in the comparator arm based on IRC assessment.
    3. Duration of complete response (DOCR), defined as the time between the date of a first CR and the date of assessment of objective disease
    progression or the date of death due to DLBCL, whichever occurs first, based on IRC assessment.
    4. Overall survival (OS), defined as time between the date of randomisation and the date of death of any cause.
    Other Secondary Endpoints:
    • PFS rates at 6 and at 12 months based on investigator assessment and based on IRC assessment.
    • PFS based on investigator assessment.
    • EFS based on investigator assessment.
    • EFS rates at 6 and at 12 months based on investigator assessment and based on IRC assessment.
    • Modified EFS (mEFS) defined as the time between the date of randomisation and the date of the event (start of new anti-lymphoma therapy or death of any cause).
    • BCRR, defined as the proportion of participants with at least one CR assessment until Week 24 in the MB-CART2019.1 arm and Week 26 in
    the comparator arm based on investigator assessment.
    • BCRR until Week 48 in the MB-CART2019.1 arm and Week 50 in the comparator arm based on investigator assessment and based on IRC
    assessment.
    • Modified BCRR (mBCRR), defined as the proportion of participants with at least one CR assessment without symptoms (B symptoms,
    symptomatic splenomegaly, symptomatic hepatomegaly, symptomatic lymphadenopathy and infections) at the time of this CR based on
    investigator assessment and based on IRC assessment.
    • DOCR, defined as the time between the date of a first CR and the date of assessment of objective disease progression or the date of death due
    to DLBCL, whichever occurs first, based on investigator assessment.
    • Duration of response (DOR), defined as the time between the date of a first objective response (CR/partial response [PR]) and the date of
    assessment of objective disease progression or the date of death due to DLBCL, whichever occurs first, based on investigator assessment and
    based on IRC assessment.
    • Time to objective response (TTR), defined as the time between the date of randomisation and the date of a first objective response (CR/PR)
    based on investigator assessment and based on IRC assessment.
    • Time to complete response (TTCR), defined as the time between the date of randomisation and the date of a first objective CR based on
    investigator assessment and based on IRC assessment.
    • Time to modified complete response (TTmCR), defined as the time between the date of randomisation and the date of a first objective CR
    without symptoms (B symptoms, symptomatic splenomegaly, symptomatic hepatomegaly, symptomatic lymphadenopathy and
    infections) at the time of this CR based on investigator assessment and based on IRC assessment.
    • Objective response rate (ORR), defined as the proportion of participants with either a CR or PR based on investigator assessment
    and based on IRC assessment.
    • Complete response rate (CRR), defined as the proportion of participants with a CR based on investigator assessment and based on
    IRC assessment.
    • Best objective response (BOR), defined as the best objective response in the time between the date of randomisation and the date of objective
    disease progression, the start of new anti-lymphoma therapy or the date of death from any cause, whichever occurs first, based on investigator
    assessment and based on IRC assessment.
    • Change in B symptoms (recurrent, unexplained fever > 38 °C without signs of infection, drenching night sweats without signs of infection
    and/or unintentional weight loss ≥ 10% within the preceding 6 months), defined as the proportion of participants with B symptoms at baseline
    and with changes in B symptoms from baseline at any time following randomisation.
    • Changes in HRQoL.
    • Changes in lymphoma symptoms
    In MB-CART2019.1 arm only:
    • Persistence of MB-CART2019.1 and phenotype and immune cell compositions based on flow cytometry analyses and real time
    quantitative polymerase chain reaction (qPCR).
    • Types and levels of cytokines (including sIL-2R, IL 6, IL-10, IL-15, IFN-γ and TFNα).
    • Anti-MB-CART2019.1 antibody.
    FOR FULL LIST OF SECONDARY ENDPOINTS, PLEASE REFER TO THE STUDY PROTOCOL
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. The time between the date of randomisation and the date of the event.
    2. The proportion of participants with at least one complete response assessment until Week 24 in the MB-CART2019.1 arm and Week 26 in
    the comparator arm based on IRC assessment.
    3. The time between the date of a first complete response (CR) and the date of assessment of objective disease progression or the date of death
    due to DLBCL, whichever occurs first, based on IRC assessment.
    4. The time between the date of randomisation and the date of death of any cause.
    FOR FULL LIST OF TIMEPOINTS OF EVALUATION, PLEASE REFER TO THE STUDY PROTOCOL
    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 No
    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 Yes
    E.8.1.1Randomised Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned15
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Day when the last participant completes the last assessment, is considered lost to follow-up, withdraws consent or dies.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    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: 117
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 51
    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 state56
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 168
    F.4.2.2In the whole clinical trial 168
    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)
    Up to 2 years after dosing regular follow-up visits will be performed.
    The treating physician assesses the post treatment options of the individual patient; e.g. regular treatment with licensed chemotherapeutic or immunotherapeutic agents, possibility to
    participate in further investigational trials and/or treatment on a named patient basis.
    After completion of the follow-up, patients will be invited to participate in a subsequent long-term follow up (LTFU) study for up to 13 more years.
    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 Decision2021-08-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-06
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA