Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients

NCT04844866 | Recruiting Phase 2

• 1 other identifier: M-2020-371
• Study Type: interventional
• Target: 213
• Locations: 14 countries
• Sites: 52

Brief Summary

In the current protocol version, there are two parts. Part I is 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, who are not eligible for high-dose chemotherapy and autologous stem cell transplantation. Part II is a Phase II single-arm, open-label, multi-centre study evaluating the efficacy and safety of MB-CART2019.1 in younger, fit participants with R-R DLBCL. Part II will start after completion of enrolment in Part I.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

CAR T cells; chimeric antigen receptor; MB-CART2019.1; CD20; CD19; relapsed refractory; Diffuse Large B-cell Lymphoma; DLBCL; Non-Hodgkin Lymphoma; NHL; zamtocabtagene autoleucel; blood cancer; LBCL; Follicular Lymphoma 3B

Outcome Measures

Primary Outcomes (2)

• Part I: Event-free survival

  Event-free survival (EFS), defined as the time between the date of randomisation and the date of objective disease progression, failure to achieve partial response (PR) or complete response (CR) at or beyond Week 8 after randomisation leading to a new anti-lymphoma therapy or death of any cause, whichever occurs first, based on independent review committee (IRC) assessment.

  up to 30 weeks after randomisation

• Part II: Best objective response rate

  Best objective response rate (BORR), defined as the proportion of participants with at least one CR or PR between the date of MB-CART2019.1 infusion 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 IRC assessment.

  up to 30 weeks after administration of MB-CART2019.1

Secondary Outcomes (9)

• Part I: Progression-free survival (PFS)

  up to 99 weeks after randomisation

• Part I: Best complete response rate

  up to 99 weeks after randomisation

• Part I: Duration of complete response

  up to 91 weeks

• Part I: Overall Survival

  up to 99 weeks after randomisation

• Part II: Duration of Response (DOR)

  up to 91 weeks

Study Arms (3)

Part I: CAR T-cell MB-CART2019.1

EXPERIMENTAL

Single infusion of 2.5 × 10\^6 CAR-transduced autologous T cells per kg/body weight.

Genetic: MB-CART2019.1

Part II: CAR T-cell MB-CART2019.1

EXPERIMENTAL

Single infusion of 2.5 × 10\^6 CAR-transduced autologous T cells per kg/body weight.

Genetic: MB-CART2019.1

PART I: Standard of Care

ACTIVE COMPARATOR

R-GemOx R-Pola

Drug: Standard of Care

Interventions

MB-CART2019.1 GENETIC

MB-CART2019.1 is designed to effectively target malignant B cells in patients suffering from late stage haematological B-cell malignancies. MB-CART2019.1 consists of autologous cluster of differentiation CD20/CD19 chimeric antigen receptor (CAR) transduced CD4/CD8 enriched T cells, derived from a leukapheresis and processed by using the CliniMACS Prodigy® device.

Also known as: Zamtocabtagene Autoleucel, Zamto-cel

Part I: CAR T-cell MB-CART2019.1; Part II: CAR T-cell MB-CART2019.1

Standard of Care DRUG

Standard of Care

Also known as: Rituximab, Gemcitabine, Oxaliplatin, Polatuzumab vedotin, Bendamustine, Rituximab

PART I: Standard of Care

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Contraindications for R-GemOx, BR plus polatuzumab vedotin, cyclophosphamide and fludarabine as judged by the treating physician.
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
• Participants who have received more than one line of treatment for DLBCL or associated subtypes.
• Prior haematopoietic stem cell transplantation (HSCT; as first-line consolidation) \< 3 months at the time of leukapheresis.
• ECOG performance status \> 2.
• Absolute neutrophil count \< 1,000/μL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow biopsy).
• Platelet count \< 50,000/μL (unless secondary to bone marrow involvement by DLBCL as demonstrated by bone marrow biopsy).
• Absolute lymphocyte count \< 100/μL.
• Participants who have central nervous system (CNS) lymphoma involvement in present or past medical history.
• Participants with the requirement for urgent therapy due to tumour mass effects.
• Infection with human immunodeficiency virus.
• 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.
• Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Active, severe systemic fungal, viral or bacterial infection.
• Known history or evidence of severely immunocompromised state, i.e. corticosteroid treatment \> 10 mg/day for more than 6 months.

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead
• ICON plc: collaborator

Study Sites (52)

LKH - Medizinische Universitaet Graz

Graz, 8036, Austria

ACTIVE NOT RECRUITING

Universitatsklinikum Innsbruck Universitatsklinik fur Innere Medizin V

Innsbruck, 6020, Austria

RECRUITING

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

RECRUITING

Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH)

Vienna, 1090, Austria

RECRUITING

Jules Bordet lnstitute

Anderlecht, 1070, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

University Hospital Center Zagreb

Zagreb, 10000, Croatia

NOT YET RECRUITING

University Hospital Hradec Kralove

Hradec Králové, 50005, Czechia

COMPLETED

FNsP Ostrava

Ostrava, 70852, Czechia

COMPLETED

Helsinki University Comprehensive Cancer Center

Helsinki, 00029, Finland

NOT YET RECRUITING

Oulu University Central Hospital

Oulu, 90220, Finland

NOT YET RECRUITING

Turku University Hospital

Turku, 20520, Finland

NOT YET RECRUITING

Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor

Créteil, 94010, France

RECRUITING

CHRU de Lille - Hopital Claude Huriez

Lille, 59000, France

ACTIVE NOT RECRUITING

Centre Hospitalier Lyon Sud, Hospices Civils de Lyon Groupement Hospitalier Sud

Lyon, 69495, France

ACTIVE NOT RECRUITING

Centre Paoli Calmettes

Marseille, 13273, France

RECRUITING

Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu

Nantes, 44093, France

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque

Pessac, 33600, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86000, France

RECRUITING

CHU de Rennes - Hopital de Pontchaillou

Rennes, 35033, France

RECRUITING

Institut Universitaire du Cancer Service d´hématologie

Toulouse, 31059, France

RECRUITING

CHU de Nancy Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Universitatsklinikum Augsburg

Augsburg, 86156, Germany

RECRUITING

Universitaetsklinikum Knappschaftskrankenhaus Bochum der Ruhr-Universitat Bochum

Bochum, 44892, Germany

RECRUITING

Universitaetsklinikum Koeln

Cologne, 50937, Germany

RECRUITING

Klinikum Erlangen der Friedrich-Alexander-Universitaet Erlangen-Nuernberg

Erlangen, 91054, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

RECRUITING

Klinikum der Universitat München, Studienzentrale fur Hematologie der Medizinischen Klinik II

München, 81377, Germany

RECRUITING

University Hospital Regensburg

Regensburg, 93053, Germany

RECRUITING

University Hospital of Tuebingen

Tübingen, 72076, Germany

RECRUITING

Del-Pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet

Budapest, 1097, Hungary

RECRUITING

Debreceni Egyetem - Orvos es Egeszsegtudomanyi Centrum (DEOEC) (University of Debrecen Medical and Health Science Center)

Debrecen, 4032, Hungary

RECRUITING

Azienda Ospedaliera San Giovanni Battista Di Torino

Torino, 10126, Italy

RECRUITING

Amsterdam Universitaire Medische Centra (UMC) - locatie Amsterdam Medisch Centrum (AMC)

Amsterdam, 1105 AZ, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Leiden University Medical Center (LUMC)

Leiden, 2333 ZA, Netherlands

RECRUITING

Erasmus University Medical Center

Rotterdam, 3015 GC, Netherlands

RECRUITING

Uniwersytecki Szpital Kliniczny - Klinika Hematologii, Terapii Komorkowych i Chorob Wewnetrznych

Wroclaw, 50367, Poland

ACTIVE NOT RECRUITING

Instituto Portugues de Oncologia do Porto Francisco Gentil E.P.E

Porto, 4200-072, Portugal

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona (Hospital Clinic i Provincial)

Barcelona, 08036, Spain

RECRUITING

Catalan Institute of Oncology (ICO) Hospitalet

Barcelona, 08907, Spain

RECRUITING

Hospital Clínico San Carlos (HCSC)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Virgen De La Arrixaca (Huva)

Murcia, 30120, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

NOT YET RECRUITING

American Hospital

Şişli, 34365, Turkey (Türkiye)

NOT YET RECRUITING

Koc Universitesi Hastanesi (Koc University Hospital)

Zeytinburnu, 34010, Turkey (Türkiye)

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Hematologic Neoplasms

Interventions

Standard of Care; Rituximab; Gemcitabine; Oxaliplatin; polatuzumab vedotin; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Butyrates; Acids, Acyclic; Carboxylic Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Peter Borchmann, Prof. Dr.

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Hess, Dr.

CONTACT

+49 160 9897 0124; mark.hess@miltenyi.com

Gregor Zadoyan, Dr.

CONTACT

+49 2204 8306; gregor.zadoyan@miltenyi.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Recruitment completed in Part I: unblinded 1:1 randomization into IMP or SoC (168 patients) Recruitment ongoing in Part II: unblinded, single arm, non-randomized, IMP only (approx. 45 patients)

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 14, 2021
• Study Start: August 18, 2021
• Primary Completion: January 15, 2025
• Study Completion (Estimated): September 30, 2031
• Last Updated: April 29, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2); AU (4); IT (1); PL (1); ES (7); CR (1); NL (4); TU (3); HU (2); PT (1); DE (11); BE (2); FI (3); FR (10)