Relapsed/refractory diffuse large B cell lymphoma (R-R DLBCL) MedDRA version: 21.0 Level: PT Classification code 10003903 Term: B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10003902 Term: B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Miltenyi Biomedicine GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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. RCHOP [rituximab, cyclophosphamide, daunorubicin, vincristine and prednisone]). - Progressive disease (PD) 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 = 24 months from the start of the first-line therapy. • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease progression (except where prohibited due to comorbidities) within = 24 months from the start 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 (HCTCI) > 3. OR • Age = 65 years and = 1 of the criteria below: - Impaired cardiac function (left ventricular ejection fraction [LVEF] 1. Documentation of the reason for ineligibility for ASCT must be present in the participant's source data. 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 axis;
Exclusion criteria
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) 2. 6. Absolute neutrophil count 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 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 cel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 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 (ASCT). ;Secondary Objective: • 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. For Exploratory Objectives and Exploratory Objectives for One-sided Crossover to MB-CART2019.1 see protocol;Primary end point(s): 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 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. ;Timepoint(s) of evaluation of this end point: The time between the date of randomisation and the date of objective disease progression, failure to achieve partial response (PR) or 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Efficacy Endpoints: 1. 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 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 of any cause, 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. • Time to new anti-lymphoma therapy 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 | — |
Countries
Austria, Belgium, Czech Republic, Germany, Hungary, Italy, Lithuania, Netherlands, Poland, Spain, Sweden
Contacts
Public ContactDirector Clinical Development
Miltenyi Biomedicine GmbH
Outcome results
None listed