NCT05826535

Brief Summary

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of rondecabtagene autoleucel (ronde-cel) also known as LYL314, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
270

participants targeted

Target at P75+ for phase_1

Timeline
63mo left

Started May 2023

Longer than P75 for phase_1

Geographic Reach
2 countries

31 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 Progress37%
May 2023Jun 2031

First Submitted

Initial submission to the registry

March 24, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 24, 2023

Completed
15 days until next milestone

Study Start

First participant enrolled

May 9, 2023

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2031

Last Updated

April 17, 2026

Status Verified

April 1, 2026

Enrollment Period

5.7 years

First QC Date

March 24, 2023

Last Update Submit

April 15, 2026

Conditions

Large B-cell LymphomaRelapsed Non-Hodgkin LymphomaNon-Hodgkin LymphomaRefractory Non-Hodgkin Lymphoma

Keywords

CAR T-cellNon-Hodgkin LymphomaCD19/20CD19CD20NHLDiffuse Large B-cell lymphomaDLBCLTransformed follicular lymphomaTFLPrimary mediastinal B-cell lymphomaPMBCLFollicular lymphoma Grade 3BLarge cell follicular lymphomaAggressive B-cell NHLRefractory Aggressive B-Cell LymphomaRefractory B-Cell Non-Hodgkin LymphomaLymphoma, Non-HodgkinLymphomaLymphoma, Large B-Cell, DiffuseCyclophosphamideFludarabineLymphoma, FollicularLymphoma, B-cellImmunosuppressive AgentsImmunologic FactorsDisease AttributesImmune System DiseasesRecurrencePiNACLE

Outcome Measures

Primary Outcomes (2)

  • Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent

    Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)

    Baseline to Month 24

  • Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR)

    ORR based on Independent Review Committee (IRC) assessment per Lugano criteria

    Baseline to Month 24

Secondary Outcomes (10)

  • Phase 1: Evaluate the efficacy of ronde-cel

    Baseline to Month 24

  • Phase 1: Evaluate the feasibility of treatment with ronde-cel

    Baseline to Month 24

  • Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent

    Baseline to Month 24

  • Phase 2: Estimate the efficacy of ronde-cel

    Baseline to Month 24

  • Phase 2: Estimate the efficacy of ronde-cel

    Baseline to Month 24

  • +5 more secondary outcomes

Study Arms (6)

Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)

EXPERIMENTAL
Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)

EXPERIMENTAL
Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)

EXPERIMENTAL
Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)

EXPERIMENTAL
Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)

EXPERIMENTAL
Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)

EXPERIMENTAL

Single dose determined during Phase 1.

Drug: Rondecabtagene autoleucel (ronde-cel)Drug: FludarabineDrug: Cyclophosphamide

Interventions

FludarabineDRUG

Conditioning chemotherapy

Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
CyclophosphamideDRUG

Conditioning chemotherapy

Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
Rondecabtagene autoleucel (ronde-cel)DRUG

CAR T-cell therapy

Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)

Eligibility Criteria

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

You may qualify if:

  • Age 18 years or older
  • Willing and able to provide written informed consent
  • Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
  • Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
  • Relapsed or refractory disease.
  • At least 1 measurable lesion (per Lugano classification)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
  • Absolute neutrophil count (ANC) ≥ 1000/µL
  • Platelet count ≥ 50,000/µL
  • Absolute lymphocyte count (ALC) ≥ 200/µL
  • Other protocol-defined criteria apply.

You may not qualify if:

  • History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
  • Active central nervous system involvement
  • History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
  • Ongoing or impending oncologic emergency
  • Recent systemic anti-cancer therapy or radiation
  • Ongoing non-hematologic toxicities due to prior therapy
  • History of allogeneic stem cell or solid organ transplantation
  • Autologous stem cell transplantation within 6 weeks
  • History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel) (Cohort 2).
  • Primary immunodeficiency
  • History of autoimmune disease resulting in end organ injury or requiring recent therapy
  • Other protocol-defined criteria apply.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (31)

University of California-Irvine Medical Center

Irvine, California, 92697, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

University of California, Los Angeles (UCLA) Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Scripps Clinic

San Diego, California, 92037, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Augusta University Medical Center

Augusta, Georgia, 30912, United States

RECRUITING

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, 46237, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Louisville Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

Louisiana State University Health Sciences Center

Shreveport, Louisiana, 71130, United States

RECRUITING

Corewell Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Cincinnati (UC) Physicians Company, LLC

Cincinnati, Ohio, 45267, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Lehigh Valley Topper Cancer Center Institute

Allentown, Pennsylvania, 18103, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

Baylor University Medical Center

Dallas, Texas, 75246, United States

RECRUITING

Texas Transplant Institute

San Antonio, Texas, 78229, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Intermountain Healthcare

Salt Lake City, Utah, 84143, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 24502, United States

RECRUITING

Virginia Commonwealth University-Massey Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

The Alfred Hospital

Melbourne, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, FollicularLymphoma, B-CellLymphomaDisease AttributesImmune System DiseasesRecurrence

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Central Study Contacts

Stephen Simko, MD

CONTACT

000-000-0000clinicaltrials@lyell.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2023

First Posted

April 24, 2023

Study Start

May 9, 2023

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

June 30, 2031

Last Updated

April 17, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(30)AU(1)