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 diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy. Additional cohorts include subjects with B-cell primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL), mantle cell lymphoma (MCL) and Richter's transformation (RT) 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 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)
• CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)
• Mantle Cell Lymphoma (MCL) Cohort: Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation
• Richter's Transformation (RT) Cohort: Histologically confirmed Richter's transformation (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 failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT
• Chemotherapy-refractory disease 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
• CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) at least first-line 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
• No contraindications for MRI evaluation
• MCL Cohort: Subjects with relapsed/refractory disease after at least one prior systemic treatment, that must include:
• Cytotoxic rituximab-based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND

+ 18 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:
• Midline shift on MRI
• Abnormal high CSF opening pressure and or CSF protein >150 mg/dL Recent (within 3 months) whole brain radiotherapy (WBRT)
• 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

+ 8 more criteria — see the full checklist in the app.

Where this trial is running

• 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
• 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
• University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, United States
• Dana Farber Cancer Institute, Boston, Massachusetts, United States

+ 13 more sites.

Who to contact

Bryan Dumont · 617-218-0044 · clinicaltrials@miltenyi.com

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