A Pivotal Phase II Randomised, Multi-centre, Open-label Study to Evaluate the Efficacy and Safety of MB-CART2019.1 Compared to SoC Therapy in Participants With r/r DLBCL, Who Are Not Eligible for HDC and ASCT
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Diffuse Large B-cell Lymphoma
- Sponsor
- Miltenyi Biomedicine GmbH
- Enrollment
- 45
- Locations
- 52
- Primary Endpoint
- Part I: Event-free survival
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
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.
Detailed Description
In Part I, the 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. In Part II, the study should evaluate the efficacy of MB-CART2019.1 in younger, fit participants with R-R DLBCL. Approximately 45 participants will be enrolled in this part to obtain 40 evaluable participants for the analysis of the primary endpoint. Screening will take place within 4 weeks before leukapheresis. In individual cases, the sponsor may agree to extending the screening period by up to two weeks. Only participants satisfying all protocol inclusion and none of the exclusion criteria will be included in the clinical study.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Part I: Event-free survival
Time Frame: 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.
Part II: Best objective response rate
Time Frame: up to 30 weeks after administration of MB-CART2019.1
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.
Secondary Outcomes
- 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)
- Part II: Progression-free survival (PFS)(up to 99 weeks after leukapheresis)
- Part II: Overall Survival (OS)(up to 99 weeks after leukapheresis)
- Part II: Best Complete Response Rate (BCRR)(up to 99 weeks after leukapheresis)
- Part II: Duration of Complete Response (DOCR)(up to 91 weeks)