Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Genetic: MB-CART2019.1Drug: R-GemOx or BR plus polatuzumab vedotin
- Registration Number
- NCT04844866
- Lead Sponsor
- Miltenyi Biomedicine GmbH
- Brief Summary
This 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.
- Detailed Description
This study should determine superiority of MB-CART2019.1 treatment compared to SoC therapy with R-GemOx (rituximab, gemcitabine and oxaliplatin) with respect to event-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.
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®. Patients who are suitable for this study will be randomized 1:1 to either MB-CART2019.1 or SoC. Both treatment arms are unblinded.
MB-CART2019.1 arm: Single infusion of fresh formulation of 2.5 × 10\^6 CAR-transduced autologous T cells. IMP is only to be administered after a lymphodepleting chemotherapy with fludarabine and cyclophosphamide. For MB-CART2019.1 production, patients will undergo a leukapheresis.
SoC arm: R-GemOx (8 cycles of 14 days each) or (10% of SoC arm) BR (Bendamustine/Rituximab) + polatuzumab vedotin (6 cycles of 21 days each). Participants from the SoC arm are allowed to be treated with MB-CART2019.1 upon request by the investigator if at least one of the following criteria is confirmed by the IRC:
* Relapse or progression occurring at any time within 1 year after randomisation.
* Failure to achieve PR or CR at or beyond Week 8 after randomisation (after 4 cycles of R-GemOx or 3 cycles of BR plus polatuzumab vedotin) and the start of a new anti-lymphoma therapy is warranted.
The duration of the active part of the study for each individual participant from screening to the end of the 1-year follow-up after infusion of MB-CART2019.1 cells (experimental arm) or the start of SoC therapy (comparator arm) will be approximately 55 weeks. The LTFU in Year 2 after infusion of MB-CART2019.1 cells or the start of treatment in the comparator arm will not be part of the active part of the clinical study and will be reported separately.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 168
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CAR T-cell MB-CART2019.1 MB-CART2019.1 Single infusion of 2.5 × 10\^6 CAR-transduced autologous T cells per kg/body weight. Standard of Care R-GemOx or BR plus polatuzumab vedotin Immunochemotherapy will be administered from the following 2 predefined regimens: R-GemOx (8 cycles of 14 days each) or BR plus polatuzumab vedotin (6 cycles of 21 days each). BR plus polatuzumab vedotin will be capped at a maximum of 10% of participants; i.e. a maximum of 8 participants will be randomised to the BR plus polatuzumab vedotin regimen. Participants from the SoC arm are allowed to be treated with CAR T-cell MB-CART2019.1 upon request by the investigator if at least one of the following criteria is confirmed by the IRC: * Relapse or progression occurring at any time within 1 year after randomisation. * Failure to achieve PR or CR at or beyond Week 8 after randomisation (after 4 cycles of R-GemOx or 3 cycles of BR plus polatuzumab vedotin) and the start of a new anti-lymphoma therapy is warranted. Standard of Care MB-CART2019.1 Immunochemotherapy will be administered from the following 2 predefined regimens: R-GemOx (8 cycles of 14 days each) or BR plus polatuzumab vedotin (6 cycles of 21 days each). BR plus polatuzumab vedotin will be capped at a maximum of 10% of participants; i.e. a maximum of 8 participants will be randomised to the BR plus polatuzumab vedotin regimen. Participants from the SoC arm are allowed to be treated with CAR T-cell MB-CART2019.1 upon request by the investigator if at least one of the following criteria is confirmed by the IRC: * Relapse or progression occurring at any time within 1 year after randomisation. * Failure to achieve PR or CR at or beyond Week 8 after randomisation (after 4 cycles of R-GemOx or 3 cycles of BR plus polatuzumab vedotin) and the start of a new anti-lymphoma therapy is warranted.
- Primary Outcome Measures
Name Time Method Event-free survival up to 30 weeks after randomisation 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.
- Secondary Outcome Measures
Name Time Method Best complete response rate up to 99 weeks after randomisation To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.
Progression-free survival (PFS) up to 99 weeks after randomisation 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 IRC assessment.
Duration of complete response up to 91 weeks To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.
Overall survival up to 99 weeks after randomisation To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.
Trial Locations
- Locations (53)
Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
🇪🇸Barcelona, Spain
Medizinische Universitaetsklinik Graz
🇦🇹Graz, Austria
Universitatsklinikum Innsbruck Universitatsklinik fur Innere Medizin V
🇦🇹Innsbruck, Austria
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH)
🇦🇹Wien, Austria
Jules Bordet lnstitute
🇧🇪Anderlecht, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Universite Catholique de Louvain Namur, Centre Hospitalier Universitaire Dinant Godinne Site Godinne
🇧🇪Yvoir, Belgium
University Hospital Hradec Kralove
🇨🇿Hradec Králové, Czechia
FNsP Ostrava
🇨🇿Ostrava, Czechia
Centre Hospitalier Universitaire (CHU) - Hopital Henri Mondor
🇫🇷Créteil, France
CHRU de Lille - Hopital Claude Huriez
🇫🇷Lille, France
Centre Hospitalier Lyon Sud, Hospices Civils de Lyon Groupement Hospitalier Sud
🇫🇷Lyon, France
Centre Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier Universitaire de Montpellier - Hopital Saint-Eloi
🇫🇷Montpellier, France
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu
🇫🇷Nantes, France
Hospital Saint-Louis - APHP
🇫🇷Paris, France
Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque
🇫🇷Pessac, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
CHU de Rennes - Hopital de Pontchaillou
🇫🇷Rennes, France
Institut Universitaire du Cancer Service d´hématologie
🇫🇷Toulouse, France
CHU de Nancy Hopitaux de Brabois
🇫🇷Vandœuvre-lès-Nancy, France
Universitatsklinikum Augsburg
🇩🇪Augsburg, Germany
Helios Klinikum Berlin - Buch
🇩🇪Berlin, Germany
Universitaetsklinikum Knappschaftskrankenhaus Bochum der Ruhr-Universitat Bochum
🇩🇪Bochum, Germany
Universitaetsklinikum Koeln
🇩🇪Cologne, Germany
Klinikum Erlangen der Friedrich-Alexander-Universitaet Erlangen-Nuernberg
🇩🇪Erlangen, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum der Universitat München, Studienzentrale fur Hematologie der Medizinischen Klinik II
🇩🇪München, Germany
Universitaetsklinikum Muenster
🇩🇪Münster, Germany
University Hospital Regensburg
🇩🇪Regensburg, Germany
University Hospital of Tuebingen
🇩🇪Tuebingen, Germany
Del-Pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
ðŸ‡ðŸ‡ºBudapest, Hungary
Debreceni Egyetem - Orvos es Egeszsegtudomanyi Centrum (DEOEC) (University of Debrecen Medical and Health Science Center)
ðŸ‡ðŸ‡ºDebrecen, Hungary
Azienda Ospedaliera San Giovanni Battista Di Torino
🇮🇹Torino, Italy
VUH Santaros Klinikos
🇱🇹Vilnius, Lithuania
Amsterdam Universitaire Medische Centra (UMC) - locatie Amsterdam Medisch Centrum (AMC)
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Leiden University Medical Center (LUMC)
🇳🇱Leiden, Netherlands
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu. Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
🇵🇱Wrocław, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Catalan Institute of Oncology (ICO) Hospitalet
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen De La Arrixaca (Huva)
🇪🇸Murcia, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Onkologikliniken
🇸🇪Uppsala, Sweden