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.
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.
Eligibility
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;