Study of Rondecabtagene Autoleucel in Aggressive Large B-Cell Lymphoma

a study on Lymphoma Non-Hodgkin Lymphoma

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Irvine, California and other locations
Dates
study started
study ends around

Description

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.

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

Details

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.

Keywords

Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Large B-cell Lymphoma, CAR T-cell, CD19/20, CD19, CD20, NHL, Diffuse Large B-cell lymphoma, DLBCL, Transformed follicular lymphoma, TFL, Primary mediastinal B-cell lymphoma, PMBCL, Follicular lymphoma Grade 3B, Large cell follicular lymphoma, Aggressive B-cell NHL, Refractory Aggressive B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Cyclophosphamide, Fludarabine, Lymphoma, Follicular, Lymphoma, B-cell, Immunosuppressive Agents, Immunologic Factors, Disease Attributes, Immune System Diseases, Recurrence, PiNACLE, Follicular Lymphoma, B-Cell Lymphoma, Rondecabtagene autoleucel (ronde-cel)

Eligibility

You can join if…

Open to people ages 18 years and up

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

Other protocol-defined criteria apply.

You CAN'T join if...

  1. History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
  2. Active central nervous system involvement
  3. History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
  4. Ongoing or impending oncologic emergency
  5. Recent systemic anti-cancer therapy or radiation
  6. Ongoing non-hematologic toxicities due to prior therapy
  7. History of allogeneic stem cell or solid organ transplantation
  8. Autologous stem cell transplantation within 6 weeks
  9. 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).
  10. Primary immunodeficiency
  11. History of autoimmune disease resulting in end organ injury or requiring recent therapy

Other protocol-defined criteria apply.

Locations

  • University of California-Irvine Medical Center accepting new patients
    Irvine California 92697 United States
  • University of California, Los Angeles (UCLA) Medical Center accepting new patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Lyell Immunopharma, Inc.
ID
NCT05826535
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 270 study participants
Last Updated
Contact us about this trial