Study of Rondecabtagene Autoleucel in Aggressive Large B-Cell Lymphoma
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Rondecabtagene autoleucel (ronde-cel), Fludarabine, Cyclophosphamide.
- Who it may be relevant to
- Registry conditions: Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Large B-cell Lymphoma. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of Rondecabtagene Autoleucel, a CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy in Participants With Aggressive B-Cell Non-Hodgkin Lymphoma
Overview
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.
Detailed description
This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of ronde-cel, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.
Five cohorts of participants will be enrolled:
Cohort 1: (3rd or later line, 3L+) Participants who have received least two prior lines of treatment
Cohort 2: (CAR T-cell experienced, 3L+): Participants who have received at least two prior lines of treatment including one prior CAR T.
Cohort 3: (second line, 2L) Participants with refractory disease or relapse within one year of first-line therapy (second-line).
Cohort 4: (TCE-experienced, 3L+) Participants have received prior T-cell engager therapy and have received at least two prior lines of treatment including one TCE therapy and have not received prior CAR T.
Cohort 5: (high-risk 1st line) Participants receiving first-line treatment who remain with disease on positron emission tomography scanning (PET-positive) after 2 to 3 cycles of standard-of-care chemoimmunotherapy and have not received prior CAR T.
Up to approximately 150 participants (across all cohorts) will be enrolled in the dose finding Phase 1 part of the study.
The Phase 2 pivotal study (PiNACLE) will expand enrollment of Cohort 1 to approximately 120 participants to further evaluate the safety and efficacy of ronde-cel.
Ronde-cel treatment consists of a single administration of CAR transduced autologous T-cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered over 3 days.
Individual participants will remain in the active post-treatment follow-up (PTFU) period for approximately 2 years. Participants will continue in long-term follow-up (LTFU) for 15 years from ronde-cel treatment.
Interventions
- Drug Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy - Drug Fludarabine
Conditioning chemotherapy - Drug Cyclophosphamide
Conditioning chemotherapy
Primary outcome measures
- Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR) [Time frame: Baseline to Month 24]
Secondary outcome measures (10)
- Phase 1: Evaluate the efficacy of ronde-cel [Time frame: Baseline to Month 24]
- Phase 1: Evaluate the feasibility of treatment with ronde-cel [Time frame: Baseline to Month 24]
- Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel [Time frame: Baseline to Month 24]
- Phase 2: Estimate the efficacy of ronde-cel [Time frame: Baseline to Month 72]
- Phase 2: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent [Time frame: Baseline to Month 24]
- Phase 2: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent [Time frame: Baseline to Month 24]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 32 centers
- University of California-Irvine Medical Center — Irvine
- Cedars-Sinai Medical Center — Los Angeles
- University of California, Los Angeles (UCLA) Medical Center — Los Angeles
- Scripps Clinic — San Diego
- Colorado Blood Cancer Institute — Denver
- Medstar Georgetown University Hospital — Washington D.C.
- Augusta University Medical Center — Augusta
- Indiana Blood and Marrow Transplantation — Indianapolis
- … and 24 more centers
Australia · 2 centers
- Royal Perth Hospital — Perth
- The Alfred Hospital — Melbourne
Identifiers
NCT: NCT05826535 · LYL314-101