Clinical Trials /

DALY 2.0 USA/ MB-CART2019.1 for DLBCL



This is an open label, single arm, phase II study to determine the efficacy, safety and PK (persistence) of MBCART2019.1 cells in adults with relapsed or refractory DLBCL after receiving at least two lines of therapy.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: DALY 2.0 USA/ MB-CART2019.1 for DLBCL
  • Official Title: A Multi-center Single Arm Phase II Study to Evaluate the Safety and Efficacy of Genetically Engineered Autologous Cells Expressing Anti-CD20 and Anti-CD19 Specific Chimeric Antigen Receptor in Subjects With Relapsed and/or Refractory Diffuse Large B Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: M-2018-344
  • NCT ID: NCT04792489




MB-CART2019.1Single, open label


This is an open label, single arm, phase II study to determine the efficacy, safety and PK (persistence) of MBCART2019.1 cells in adults with relapsed or refractory DLBCL after receiving at least two lines of therapy.

Detailed Description

      A prospective, single arm, open label, multi-center, phase II study of autologous T cells
      engineered against both CD19 and CD20 antigens for subjects with relapsed or refractory DLBCL
      after receiving at least two lines of therapy. The investigational agent is the MB-CART2019.1
      cells. After successful screening, subjects will undergo leukapheresis to collect product for
      manufacturing. In preparation for the fresh product infusion, subjects will undergo a
      lymphodepleting regimen with cyclophosphamide and fludarabine. Cell infusion will be
      administered intravenously at a dose of 2.5 x 106 CAR+ cells/kg body weight. The study will
      start with enrollment of 3 subjects in the lead-in safety phase, and after safety is
      evaluated, the study will continue with enrollment of the remaining subjects. Subjects will
      be followed for up to 2 years, for efficacy and safety outcomes as well as health-related
      quality of life (HRQol). Additional long-term follow-up will be conducted for participants
      under a separate long-term follow-up protocol.

Trial Arms

Single, open labelExperimental
  • MB-CART2019.1

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed DLBCL or associated subtype, defined by WHO 2016

          -  Relapsed or Refractory disease after 2 or more lines of chemotherapy including
             rituximab and anthracycline and either having failed autologous stem cell transplant
             (ASCT), or being ineligible for or not consenting to ASCT

          -  Age > 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at
             screening. ECOG performance status of 2 at screen is allowed if the decrease in
             performance status is due to DLBCL

          -  Measurable disease according to Lugano 2014 criteria for assessing FDG PET/CT in
             lymphoma (Cheson et al, 2014)

          -  Subject must have at least 10 unstained slides of tissue available prior to
             MBCART2019.1 Infusion. If archival tissue is not available, subject must be willing to
             undergo attempted repeat biopsy

          -  No clinical suspicion of CNS lymphoma

          -  If the subject has history of CNS disease, then he/she must have no signs or symptoms
             of CNS disease, have no active disease on magnetic resonance imaging (MRI) and have no
             large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and
             flow cytometry, regardless of the number of white blood cells (WBCs)

          -  If has history of cerebral vascular accident (CVA), the CVA must be greater than 12
             months prior to leukapheresis and any neurological deficits must be stable

          -  A creatinine clearance > 60mL/min

          -  Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or
             Multigated Radionuclide Angiography (MUGA)

          -  Resting O2 saturation >90% on room air

          -  Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 times the
             Upper Limit of Normal (ULN) for age

          -  Total bilirubin <1.5 mg/dl, except in individuals with Gilbert's syndrome

          -  Absolute neutrophil count > 1000/μL

          -  Absolute lymphocyte count > 100/μL

          -  Platelet count > 50,000/μL

          -  Estimated life expectancy of more than 3 months other than primary disease

          -  Subjects of child-bearing or child-fathering potential must be willing to practice
             birth control from the time of enrollment on this study until the follow-up period of
             the study.

        Exclusion Criteria:

          -  Primary CNS lymphoma

          -  Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL)

          -  Unable to give informed consent

          -  Known history of infection with human immunodeficiency virus (HIV) or active hepatitis
             B (HBsAg positive), unless confirmed to be polymerase chain reaction (PCR) negative;
             antiviral prophylaxis isrequired if HBsAg negative and anti-HBc positive

          -  Known history of infection with hepatitis C virus (anti-HCV positive) unless viral
             load is undetectable per quantitative PCR and/or nucleic acid testing

          -  Known history of active seizures or presence of seizure activities or on active,
             anti-seizure medications within the prior 12 months

          -  Known history of CVA within prior 12 months.

          -  Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic
             neuritis, or other immunologic or inflammatory disease

          -  Presence of CNS disorder that, in the judgment of the investigator, may impair the
             ability to evaluate neurotoxicity

          -  Active systemic fungal, viral, or bacterial infection

          -  Pregnant or breast-feeding woman

          -  Previous or concurrent malignancy with the following exceptions:

          -  Adequately treated basal cell or squamous cell carcinoma (adequate wound healing
             required prior to study entry)

          -  In situ carcinoma of the cervix or breast, treated curatively and without evidence of
             recurrence for at least 2 years prior to the study

          -  Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron
             or tamoxifen and in clinical remission of ≥ 2 years

          -  A primary malignancy which has been completely resected / treated with curative intent
             and in complete remission of ≥ 2 years

          -  History of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid
             arthritis, systemic lupus erythematosus)requiring systemic immunosuppressive or system
             disease modifying agents within the last 2 years

          -  Medical condition requiring prolonged use of systemic corticosteroids equivalent to
             prednisone >10 mg/day

          -  History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
             other clinically significant cardiac disease within 6 months of enrollment

          -  Concurrent radiotherapy (allow up to time of leukapheresis)

          -  Baseline dementia that would interfere with therapy or monitoring, determined using
             Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline

          -  History of severe immediate hypersensitivity reaction to any of the agents used in
             this study

          -  Refusal to participate in additional lentiviral gene therapy LTFU protocol

          -  Prior CAR-T therapy for any indication

          -  Prior allogeneic stem cell transplant for any indication

          -  Prior BITE antibodies for cancer therapy

          -  Prior T cell receptor-engineered T cell therapy
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:1 month
Safety Issue:

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:6 months
Safety Issue:
Measure:Duration of Response
Time Frame:Up to 2 years
Safety Issue:
Measure:Overall Response Rate
Time Frame:6 months
Safety Issue:
Measure:Best Overall Response
Time Frame:2 years
Safety Issue:
Measure:Progression Free Survival
Time Frame:Up to 2 years
Safety Issue:
Measure:Overall Survival
Time Frame:Up to 2 years
Safety Issue:
Measure:Pharmacokinetics of MB-CART2019.1 [Maximum concentration (Cmax)]
Time Frame:Up to 2 years
Safety Issue:
Measure:Pharmacokinetics of MB-CART2019.1 [Time to maximum concentration (Tmax)]
Time Frame:Up to 2 years
Safety Issue:
Measure:Pharmacokinetics of MB-CART2019.1 [Area under the curve (AUC)]
Time Frame:Up to 2 years
Safety Issue:


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Miltenyi Biomedicine GmbH

Trial Keywords

  • Chimeric antigen receptor
  • CAR T
  • CD19
  • CD20

Last Updated

July 14, 2021