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 - DALY 2-E

Miltenyi Biomedicine GmbH0 个研究点目标入组 168 人开始时间: 2021年4月13日最近更新: 2024年2月26日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Miltenyi Biomedicine GmbH
入组人数: 168

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

性别: All

入选标准

•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:
•Age = 18 years and
•- Prior ASCT (as first-line consolidation) or
•- Haematopoietic Cell Transplantation-specific Comorbidity Index (HCTCI) > 3.
•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 < 80%) or dyspnoea on slight activity, or
•- Eastern Cooperative Oncology Group (ECOG) performance status > 1. Documentation of the reason for ineligibility for ASCT must be present in the participant's source data.
•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;

排除标准

•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 neutrophil count < 1,000/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 cel

研究者

发起方

Miltenyi Biomedicine GmbH

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