DALY II USA/ MB-CART2019.1 for DLBCL

What this study is about

DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory B cell lymphoma (BCL). Cohorts include subjects with diffuse large B-cell lymphoma (DLBCL) after receiving at least 2 lines of therapy, primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL) after receiving at least one line of therapy, mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy, and DLBCL transplant-ineligible after receiving at least one line of therapy.

Who can join (things the study team will check)

✅ You may be able to join if…

• Histologically confirmed B-cell non-Hodgkin's lymphoma:
  • DLBCL cohort (both cohorts)
• 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)
• Primary mediastinal (thymic) large B cell lymphoma
• Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3) o CNS cohort
• B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL) o Mantle Cell Lymphoma (MCL) cohort
• Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation o Richter's Transformation (RT) cohort
• Histologically confirmed RT to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)
• Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as: For DLBCL cohort (after receiving at least two prior lines of therapy): persistent disease after failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either after failed ASCT, or ineligible, not intended for or not consenting to ASCT
• Chemotherapy-refractory disease (applies to all cohorts) is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
• Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen For disease specific cohorts added after the initial DLBCL cohort the definition of relapsed/refractory disease is as described below: CNS cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) at least first-line therapy.
• First-line therapy is defined as either high dose methotrexatebased therapy, temozolomide, high dose cytarabine, pemetrexed, lenalidomide or Bruton tyrosine kinase (BTK) inhibitor-based therapy.
• No contraindications for MRI evaluation
• CNS cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy
• Prior lines of systemic therapy should include an anti-CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and/or with or without an autologous stem cell transplant MCL cohort: Subjects with relapsed/refractory disease after at least one prior systemic treatment, that must include:
• Cytotoxic rituximab [or equivalent] based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND
• BTK inhibitor RT cohort: Subject must have relapsed/refractory disease after at least one prior systemic treatment following Richter's Transformation DLBCL transplant ineligible 2nd cohort: subject must have failure of first-line chemotherapy (including rituximab or equivalent and anthracycline).
• For this cohort subjects are considered transplant ineligible if they meet one of the following criteria:

+ 24 more criteria — see the full checklist in the app.

🚫 You may not be able to join if…

• Primary CNS lymphoma (not applicable to CNS cohort)
• Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)
• Unable to give informed consent
• Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative 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.
• Pharmacologically uncontrolled seizures.
• 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. For CNS Cohort:
  • For CNSL and DLBCL transplant-ineligible 2nd-line cohort patients that have a CNS lesion(s): Midline shift on MRI or Abnormal high CSF opening pressure and or CSF protein ≥150 mg/dL Recent (within 3 months) whole brain radiotherapy (WBRT) are exclusionary
• 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
• Severely immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
• Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day. For CNS cohort: Up to 2 mg/day dexamethasone (or equivalence) may be allowed at any time, higher doses allowed up to 7 days prior to apheresis or after apheresis until lymphodepletion.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
• Concurrent radiotherapy (allowed up to time of lymphodepletion). For prior systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled 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 or systemic gene modifying therapy for B-cell lymphoma
• Prior allogeneic stem cell transplant for any indication

+ 2 more criteria — see the full checklist in the app.

Where this trial is running

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• Mayo Clinic, Phoenix, Arizona, United States
• UC San Diego Health, La Jolla, California, United States
• Stanford University, Stanford, California, United States
• Colorado Blood Cancer Institute, Denver, Colorado, United States
• Yale University, New Haven, Connecticut, United States
• Baptist Health Miami Cancer Institute, Miami, Florida, United States
• Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
• Georgia Cancer Center at Augusta University, Augusta, Georgia, United States
• Robert H Lurie Cancer Center, Chicago, Illinois, United States
• University of Kansas Cancer Center, Westwood, Kansas, United States

+ 20 more sites.

Who to contact

Ron Gomez · 617-218-0044 · clinicaltrials@miltenyi.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT04792489.