a clinical study of allogeneic cd19/bcma car-t cells for the treatment of r/r b-cell malignant tumors

Conditions: B Cell Lymphoma; Multiple Myeloma

Summary: a single arm, open-label pilot study is designed to determine the safety and efficacy of cd19 and b-cell maturation antigen (bcma) targeted allogenic car-t cells (rn1101) in patients with relapsed/refractory b-cell or plasma cell-derived malignant tumors. 21 patients are planned to be enrolled in the dose-escalation trial. the primary objective of the study is to evaluation of the safety and feasibility of rn1101 for the treatment of relapsed/refractory b-cell or plasma cell-derived malignant tumors. the secondary objective is to evaluate the efficacy of rn1101 for the treatment of relapsed/refractory b-cell or plasma cell-derived malignant tumors. the exploratory objective is to evaluate expansion, persistence and ability of rn1101 to deplete cd19 or bcma positive cells in patients with relapsed/refractory b-cell or plasma cell-derived malignant tumors.


Eligibility criteria:
inclusion criteria: 1. willingness to participate in the trial and provision of signed informed consent. 2. patients diagnosed with b-lymphocyte or plasma cell-derived malignancies as per the 2017 revised who criteria, including acute b-lymphoblastic leukemia (b-all), and mature b-cell lymphomas such as diffuse large b-cell lymphoma (dlbcl), follicular lymphoma (fl), marginal zone lymphoma (mzl), small lymphocytic lymphoma/chronic lymphocytic leukemia (sll/cll), mantle cell lymphoma (mcl), multiple myeloma (mm), etc. 3. refractory or recurrent b-lymphocyte or plasma cell-derived malignancies, defined as failure to achieve complete remission after standard treatment, or relapse during follow-up after achieving remission with first-line or salvage therapy. 4. patients with b-cell acute lymphoblastic leukemia (all) who have achieved hematologic remission but have persistent minimal residual disease (mrd). 5. according to the revised international working group (iwg) criteria, relapsed/refractory lymphoma patients must have at least one measurable lesion with a longest diameter ≥1.5 cm. 6. 18 years and older, regardless of gender. 7. an expected survival of ≥12 weeks. 8. serum total bilirubin level \< twice the upper limit of normal, serum creatinine level \< upper limit of normal, serum alanine aminotransferase (alt) and aspartate aminotransferase (ast) \< three times the upper limit of normal. 9. absolute neutrophil count ≥0.5×10⁹/l, platelets ≥20×10⁹/l; for b-lymphocyte malignancies with definitive bone marrow involvement, no requirements for neutrophil and platelet counts. 10. ecog performance status of 0 - 2. 11. left ventricular ejection fraction (lvef) ≥50% and no pericardial effusion. 12. at least 2 weeks have passed since the last treatment (radiotherapy, chemotherapy, monoclonal antibody therapy, or other treatments). exclusion criteria: 1. known allergies, hypersensitivity, intolerance, or contraindications to cd19/bcma allogenic car-t or any components of the trial drugs (including fludarabine, cyclophosphamide, and rituximab), or a history of severe allergic reactions. 2. recurrence after allogeneic hematopoietic stem cell transplantation with active graft - versus - host disease (gvhd) requiring steroid or immunosuppressive therapy. 3. severe active infection. 4. acquired or congenital immunodeficiency. 5. new york heart association (nyha) class ⅲ or ⅳ heart failure. 6. history of epilepsy or other central nervous system diseases. 7. lymphoma with extranodal involvement of the brain, lungs, or gastrointestinal tract. 8. other primary cancers, except: 1. non-melanoma skin cancer (e.g., basal cell carcinoma) cured by resection. 2. carcinoma in situ (e.g., cervical, bladder, or breast cancer) cured. 9. systemic high-dose steroids within 2 weeks before treatment. 10. pregnant, breastfeeding, or plans to become pregnant within 6 months. 11. participation in another clinical trial within the past month. 12. any situation the investigator deems may raise risks or interfere with trial results.