RN1701 Injection in the Treatment of Relapsed/Refractory B-Cell Lymphomas

Exclusion Criteria

• •Subjects with any of the following conditions are ineligible for this trial:
• •1. Any malignancy other than B-cell non-Hodgkin lymphoma ever diagnosed or treated, except:
• •* Malignancy that received curative therapy and has shown no evidence of active disease for ≥2 years before enrolment; or
• •* Adequately treated non-melanoma skin cancer with no current evidence of disease.
• •2. Prior anti-cancer therapy within the stated windows (before lymphodepletion):
• •* CNS prophylaxis (e.g., intrathecal methotrexate and/or cytarabine) within 7 days;
• •* Cytotoxic chemotherapy or radiotherapy within 14 days;
• •* Small-molecule targeted or epigenetic therapy within 14 days or 5 half-lives, whichever is longer;
• •* Monoclonal antibody, bispecific antibody, or antibody-drug conjugate within 21 days or 5 half-lives, whichever is shorter;
• •* Investigational drug or invasive investigational device within 28 days (if the therapy is also investigational, the 28-day wash-out applies);
• •* Autologous haematopoietic stem-cell transplant or CD19-directed autologous CAR-T therapy within 100 days.
• •3. Any autologous cellular or gene therapy other than CD19-directed autologous CAR-T.
• •4. Any allogeneic cellular (including CAR-T) or gene therapy.
• •5. Prior allogeneic haematopoietic stem-cell transplantation.
• •6. Positive donor-specific antibody (DSA).
• •7. At least one of the following high-risk features:
• •* Sum of the product of perpendicular diameters (SPD) of all measurable lesions ≥100 cm²;
• •* Bulky disease: single mass ≥7.5 cm; mediastinal mass with maximum diameter \>1/3 of thoracic diameter;
• •* Obstructive/compressive emergency (e.g., bowel obstruction, vascular compression) requiring urgent intervention at screening.
• •8. Active CNS involvement (symptomatic or positive CSF/imaging); subjects with prior CNS disease now in remission (asymptomatic with negative CSF and imaging) are eligible.
• •9. Significant bleeding diathesis: gastrointestinal bleeding, haemorrhagic cystitis, coagulopathy, hypersplenism (splenomegaly on exam/US, cytopenias, hyperplastic marrow) or ongoing anticoagulation.
• •10. Chronic concomitant systemic corticosteroids or other immunosuppressants, except: topical, ocular, intra-articular, nasal or inhaled corticosteroids; short-course steroids for prophylaxis (e.g., contrast allergy).
• •11. Severe underlying medical conditions:
• •* Active serious viral, bacterial or uncontrolled systemic fungal infection;
• •* Active systemic autoimmune disease requiring therapy.
• •12. Significant cardiac disease:
• •* NYHA class III or IV congestive heart failure;
• •* Myocardial infarction or CABG within 6 months before enrolment;
• •* Clinically relevant ventricular arrhythmia or unexplained syncope not vasovagal or dehydration-related;
• •* Severe non-ischaemic cardiomyopathy;
• •* Left ventricular ejection fraction (LVEF) \<45% by echo or MUGA within 4 weeks before lymphodepletion.
• •13. Resting oxygen saturation \<92%.
• •14. Clinically relevant prior or current CNS disorder: epilepsy, seizure-like episodes, paralysis, aphasia, stroke, severe head trauma, dementia, Parkinson's disease, cerebellar disorder, organic brain syndrome or major psychiatric illness.
• •15. Live-attenuated vaccine within 4 weeks before screening.
• •16. Major surgery within 2 weeks before screening or planned within 2 weeks after study treatment (local anaesthesia allowed).
• •17. Positive screen for HBsAg, HBeAg, HBV DNA, HCV antibody, HCV RNA, or HIV antibody.
• •18. Life-threatening allergy, hypersensitivity or intolerance to study-drug excipients including, but not limited to, DMSO.
• •19. Lactating women.
• •20. Any condition that, in the investigator's opinion, renders the subject unsuitable for the study.