A Study to Evaluate the Safety and Effectiveness of Autologous Cells Expressing Anti-CD20 and Anti-CD19 in Relapsed/Refractory Diffuse Large B Cell Lymphoma Patients

Overview

About this study

The purpose of this study is to determine the effectiveness of MB-CART2019.1 cells administered following a conditioning lymphodepletion regimen in diffuse large B cell lymphoma (DLBCL) subjects who failed at least two lines of therapy as measured by objective response rate (ORR) at one month.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
    • DLBCL not otherwise specified (NOS);
    • High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;
    • High-grade B cell lymphoma, NOS o Primary mediastinal (thymic) large B cell lymphoma;
    • Transformed lymphoma (e.g., transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3).
  • 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 2.1.
  • Chemotherapy-refractory disease is defined as one of the following:
    • No response to last line of therapy:
    • Progressive disease (PD) as best response to most recent therapy regimen o Stable disease (SD) as best response to most recent therapy with duration no longer than 6 months from last dose of therapy; OR
    • Relapsed or persistent disease after prior ASCT for lymphoma;
      • Disease progression or relapse less than or equal to 12 months of ASCT;
      • If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
  • Disease relapse in subjects without prior ASCT is defined as relapse of disease in ≤ 12 month after the last dose of most recent therapy regimen.
  • Ineligible for ASCT is defined as meeting one of the following criteria:
    • Chemotherapy-refractory disease after salvage therapy;
    • Disease progression or relapse ≤ 12 months after salvage therapy;
    • Intolerance to salvage therapy.
  • In addition, all subjects must have:
    • 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);
    • CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however:
      • Subject must have at least 10 unstained slides of tissue available prior to MB-CART2019.1 infusion;
      • If archival tissue is not available, subject must be willing to undergo attempted repeat biopsy.
    • No clinical suspicion of central nervous system (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);
    • 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 event must be greater than 12 months prior to leukapheresis;
    • Any neurological deficits must be stable.
  • A creatinine clearance (as estimated by direct urine collection) > 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) 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 is required 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 seizure 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 active 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 is 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 systemic 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 long-term follow-up (LTFU) protocol.
  • Prior CAR-T therapy for any indication.
  • Prior allogeneic stem cell transplant for any indication.
  • Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy.
  • Prior T cell receptor-engineered T cell therapy.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Allison Rosenthal, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Patrick Johnston, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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CLS-20523445

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