NCT04792489

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 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
248

participants targeted

Target at P75+ for phase_2

Timeline
33mo left

Started May 2021

Longer than P75 for phase_2

Geographic Reach
2 countries

25 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress65%
May 2021Dec 2028

First Submitted

Initial submission to the registry

February 25, 2021

Completed
14 days until next milestone

First Posted

Study publicly available on registry

March 11, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

May 25, 2021

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

April 24, 2025

Status Verified

April 1, 2025

Enrollment Period

5.6 years

First QC Date

February 25, 2021

Last Update Submit

April 21, 2025

Conditions

Keywords

CD19/CD20-directed CAR-T CellsZamtocabtagene autoleucelB-Cell Non-Hodgkin LymphomaPrimary Central Nervous System LymphomaSecondary Central Nervous System LymphomaNHLPCNSLSCNSLChimeric Antigen ReceptorCARCAR-T CellAutologous T Cell TherapyCentral Nervous System NeoplasmsLymphomaLymphoma, Non-HodgkinLymphoma, B-CellLymphoma, Large B-Cell, DiffuseMCLRTCLLImmunotherapyT cellsT cell infusion

Outcome Measures

Primary Outcomes (1)

  • Overall Response Rate

    ORR

    through study completion, up to 2 years

Secondary Outcomes (14)

  • Complete Response Rate

    1 and 6 months

  • Duration of Response

    Up to 2 years

  • Overall Response Rate

    1 and 6 months

  • Best Overall Response

    2 years

  • Progression Free Survival

    Up to 2 years

  • +9 more secondary outcomes

Study Arms (1)

Single, open label

EXPERIMENTAL
Biological: zamtocabtagene autoleucel (MB-CART2019.1)Drug: CyclophosphamideDrug: FludarabineDrug: Bendamustine

Interventions

Chimeric antigen receptor (CAR) T cell therapy

Single, open label

Lymphodepleting chemotherapy

Single, open label

Lymphodepleting chemotherapy

Single, open label

Lymphodepleting chemotherapy

Single, open label

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify 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
  • +23 more criteria

You may not qualify 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
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

UC San Diego Health

La Jolla, California, 92037, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Baptist Health Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Robert H Lurie Cancer Center

Chicago, Illinois, 60611, United States

RECRUITING

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

TERMINATED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center - Division of Hematologic Malignancies

Durham, North Carolina, 27705, United States

RECRUITING

The Ohio State University Wexner Medical Center James Cancer

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health and Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

Allegheny Health Network Cancer Institute

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

University of Pittsburgh - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15260, United States

WITHDRAWN

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

University of Alberta Cross Cancer Institute

Edmonton, Alberta, AB T6G 1Z2, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, ON M5G 2C4, Canada

RECRUITING

Related Links

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellLymphoma, B-CellCentral Nervous System NeoplasmsLymphomaLymphoma, Non-Hodgkin

Interventions

CyclophosphamidefludarabineBendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNervous System NeoplasmsNeoplasms by SiteNervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsButyratesAcids, AcyclicCarboxylic AcidsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Johanna Theruvath, MD

    Miltenyi Biomedicine GmbH

    STUDY DIRECTOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 25, 2021

First Posted

March 11, 2021

Study Start

May 25, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Last Updated

April 24, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations