Targeting CD19/CD20 Dual-targeted Cell in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

Official title

A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LUCAR-E9D,LUCAR-E9K, a Dual-targeted Cell Product Targeting CD19/CD20, in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

Overview

A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LUCAR-E9D,LUCAR-E9K, a dual-targeted cell preparation targeting CD19/CD20, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

Detailed description

This is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LUCAR-E9D,LUCAR-E9K in the patient ≥ 18 years of age with relapsed or refractory B-cell non-Hodgkin lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LUCAR-E9D,LUCAR-E9K injection. The study will include the following sequential phases: screening, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.

Interventions

• Biological LUCAR-E9D or LUCAR-E9K cells product
  Prior to infusion of the LUCAR-E9D or LUCAR-E9K cells product subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine

Primary outcome measures

• Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events) [Time frame: 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Pharmacokinetics in peripheral blood [Time frame: 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Pharmacokinetics in bone marrow [Time frame: 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• The recommended Phase II dose (RP2D) for this cell therapy [Time frame: 30 days after LUCAR-E9D,LUCAR-E9K infusion]

Secondary outcome measures (7)

• Overall Response Rate (ORR) [Time frame: Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Progression-free survival (PFS) [Time frame: Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Overall Survival (OS) [Time frame: Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Time to Response (TTR) [Time frame: Through study completion, minimum 2 years after LUCAR-E9D,LUCAR-E9K infusion (Day 1)]
• Time to Response (TTR) [Time frame: Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion]
• Duration of Response (DoR) [Time frame: Through study completion, minimum 2 years after LUCAR-E9D,LUCAR-E9K infusion (Day 1)]
• Immunogenicity assessment of LUCAR-E9D or LUCAR-E9Kcells [Time frame: Through study completion, 2 years after LUCAR-E9D,LUCAR-E9K infusion]

Eligibility criteria

Inclusion criteria

• Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures and have signed informed consent.
• Aged 18-75 years (inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed B-cell non-Hodgkin Lymphoma that expresses at least one of CD19/CD20.
• At least one evaluable tumor lesion according to Lugano 2014 criteria.
• Response to prior therapy is consistent with one of the following:

1） Patients with B-NHL who are primary refractory and are unsuitable or unwilling to receive autologous CAR-T cell therapy; 2） primary refractory is defined as the best response to first-line treatment being SD or PD; 3） Relapse within 12 months after achieving CR with first-line chemotherapy and immunotherapy; 7. Life expectancy≥ 3 months 8. Women of childbearing potential must have a negative highly sensitive serum pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) at screening and before the first administration of cyclophosphamide and fludarabine treatment;

Exclusion criteria

• Diagnosed with or treated for other invasive malignancies besides B-cell non-Hodgkin lymphoma.
• Active acute or chronic graft-versus-host disease (GVHD), except for grade 1 skin involvement; or requiring immunosuppressive treatment for GVHD within 4 weeks prior to enrollment;
• Active CNS involvement (symptomatic or positive cerebrospinal fluid or imaging data), prior CNS infiltration but currently in remission (asymptomatic and negative cerebrospinal fluid and/or imaging data) is eligible;
• Significant bleeding tendency, such as gastrointestinal bleeding, hemorrhagic cystitis, coagulopathy.
• Chronic diseases treated with steroids or other immunosuppressants. The following situations are excluded: use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylaxis;
• Severe underlying diseases, such as: - Evidence of severe active viral, bacterial infections, or uncontrolled systemic fungal infections; - Active or unstable autoimmune diseases, or autoimmune diseases within the past 3 years with potential for relapse;
• Breastfeeding women;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• The First Affiliated Hospital of USTC (Anhui Provincial Hospital) — Hefei
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an
• Affiliated Hospital of Xuzhou Medical University — Xuzhou

Identifiers

NCT: NCT07093411 · LB2406-0001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗