Recruiting
Phase 2

MB-CART2019.1

Sponsor:

Miltenyi Biomedicine GmbH

Code:

NCT04792489

Conditions

Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Relapsed Diffuse Large B Cell Lymphoma

High Grade B-cell Lymphoma (HGBCL)

Primary Mediastinal B-cell Lymphoma (PMBCL)

Transformed Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

zamtocabtagene autoleucel (MB-CART2019.1)

Cyclophosphamide

Fludarabine

Bendamustine

Study Details

Brief summary:

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.

Conditions

Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Relapsed Diffuse Large B Cell Lymphoma

High Grade B-cell Lymphoma (HGBCL)

Primary Mediastinal B-cell Lymphoma (PMBCL)

Transformed Lymphoma

Study ID

NCT04792489

Start date

May 25, 2021

Status verified date

Jul, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:
  • Age ≥70 years
  • ECOG status is 2 at screening
  • Impaired pulmonary function: diffusing capacity of the lung for carbon monoxide \[DLCO\] ≤ 60% adjusted for gender-specific hemoglobin concentration (Coates formula)
  • Impaired cardiac function: left ventricular ejection fraction (LVEF) < 50%; must be assessed by echocardiogram or multiple uptake gated acquisition (MUGA) scan performed within 4 weeks of determination of eligibility
  • Impaired renal function: calculated creatinine clearance (Cockcroft and Gault) < 60 mL/min
  • Impaired hepatic function: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN)

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 lymphoma

  • Subjects in DLBCL transplant-ineligible 2nd-line cohort with ECOG performance status of 2, regardless of attribution, will be allowed for inclusion
  • Measurable disease will be assessed by FDG-PET/CT in systemic lymphoma . and by brain/spine MRI for CNS disease
  • Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses
  • No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)

  • Subjects in DLBCL transplant-ineligible 2nd-line cohort with SCNSL will be allowed for inclusion
  • If the subject has history of CNS disease (not applicable to CNS cohort), 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), 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 or Cockcroft-Gault Equation) > 45mL/min
  • Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
  • Subjects in DLBCL transplant-ineligible 2nd-line cohort with a lower ejection fraction of > 40% will be allowed for inclusion
  • 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
  • Subjects in DLBCL transplant-ineligible 2nd-line cohort with a total bilirubin of < 2.0 mg/dL will be allowed for inclusion
  • Absolute neutrophil count (ANC) > 1000/μL
  • Absolute lymphocyte count > 100/μL
  • Platelet count > 50,000/µL
  • Estimated life expectancy of more than 3 months other than primary disease

Exclusion Criteria:

  • 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
  • Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy
  • Prior T cell receptor-engineered T cell therapy

Study Design

Enrollment

315 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Single, open label

Interventions

zamtocabtagene autoleucel (MB-CART2019.1)

Chimeric antigen receptor (CAR) T cell therapy

Cyclophosphamide

Lymphodepleting chemotherapy

Fludarabine

Lymphodepleting chemotherapy

Bendamustine

Lymphodepleting chemotherapy

Primary outcome measure

  • Objective Response Rate [ Time Frame: through study completion, up to 2 years ]

Central Contacts and Locations

Central contacts

Ron Gomez

617-218-0044clinicaltrials@miltenyi.com

Harshita Gahankari

617-218-0044clinicaltrials@miltenyi.com

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Antwain Johnson

antwaindjohnson@uabmc.edu

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Contacts

Yasmin Adam

Yasmin.Adam2@bannerhealth.com

Mayo Clinic

Recruiting

Phoenix, Arizona, United States, 85054

Contacts

Allison Rosenthal, DO

Rosenthal.Allison@mayo.edu

UC San Diego Health

Recruiting

La Jolla, California, United States, 92037

Contacts

Dimitrios Tzachanis, MD

dtzachanis@health.ucsd.edu

Stanford University

Recruiting

Stanford, California, United States, 94305

Contacts

Christina Tran

ctran13@stanford.edu

Colorado Blood Cancer Institute

Recruiting

Denver, Colorado, United States, 80218

Contacts

Luke Mountjoy, MD

luke.mountjoy@healthonecares.com

Yale University

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Jialing Zhang

jialing.zhang@yale.edu

Baptist Health Miami Cancer Institute

Recruiting

Miami, Florida, United States, 33176

Contacts

Sueanna Sukie

Sueanna.Sukie@baptisthealth.net

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Amelia Langston, MD

alangst@emory.edu

Georgia Cancer Center at Augusta University

Recruiting

Augusta, Georgia, United States, 30912

Contacts

Vamsi Kota, MD

vkota@augusta.edu

Robert H Lurie Cancer Center

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Reem Karmali, MD

reem.karmali@northwestern.edu

University of Kansas Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Sunil Abhyankar, MD

sabhyankar@kumc.edu

University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Nancy Hardy, MD

nhardy1@umm.edu

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Obed Posada Villanueva

Obed_villanueva@DFCI.HARVARD.EDU

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Maria Hollobaugh

mholloba@med.umich.edu

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Patrick Johnston, MD

johnston.patrick@mayo.edu

Washington University, St. Louis

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Amanda Cashen, MD

acashen@wustl.edu

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Miguel-Angel Perales, MD

peralesm@mskcc.org

Duke University Medical Center - Division of Hematologic Malignancies

Recruiting

Durham, North Carolina, United States, 27705

Contacts

Matthew S. McKinney, MD

Matthew.mckinney@duke.edu

The Ohio State University Wexner Medical Center James Cancer

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Nathan Denlinger, DO

nathan.denlinger@osumc.edu

Oregon Health and Science University Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97239

Contacts

Richard Maziarz, MD

maziarzr@ohsu.edu

Allegheny Health Network Cancer Institute

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Contacts

John Lister, MD

john.lister@ahn.org

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Krish Patel, MD

krish.patel@scri.com

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

Farrukh Awan, MD

Farrukh.awan@utsouthwestern.edu

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Luhua (Michael) Wang, MD

Miwang@mdanderson.org

Texas Transplant Institute

Recruiting

San Antonio, Texas, United States, 98109

Contacts

Timothy Fenske, MD

timothy.fenske@hcahealthcare.com

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Jordan Gauthier, MD

jgauthier@fredhutch.org

Froedtert Hospital and the Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Jessica Eisenhauer

jeisenhauer@mcw.edu

University of Alberta Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, AB T6G 1Z2

Contacts

Michael Chu, MD

michael.chu@albertahealthservices.ca

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, ON M5G 2C4

Contacts

John Kuruvilla

John.Kuruvilla@uhn.ca

More Information

Sponsor

Miltenyi Biomedicine GmbH

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Keywords

  • CD19/CD20-directed CAR-T Cells
  • Zamtocabtagene autoleucel
  • B-Cell Non-Hodgkin Lymphoma
  • Primary Central Nervous System Lymphoma
  • Secondary Central Nervous System Lymphoma
  • NHL
  • PCNSL
  • SCNSL
  • Chimeric Antigen Receptor
  • CAR
  • CAR-T Cell
  • Autologous T Cell Therapy
  • Central Nervous System Neoplasms
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • MCL
  • RT
  • CLL
  • Immunotherapy
  • T cells
  • T cell infusion
  • transplant-ineligible 2nd line DLBCL

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Miltenyi Biomedicine GmbH on 2026-07-13.