RN1201injection for Relapsed/Refractory CD19+/BCMA+ Hematologic Malignancies

An Exploratory Clinical Study on the Safety and Efficacy of Allogeneic CAR-T Cell (RN1201) for Relapsed/Refractory CD19+/BCMA+ Hematologic Malignancies

This single-arm, dose-escalation exploratory trial evaluates the safety and efficacy of Allogeneic CAR-T (UCAR-T) cell therapy in patients with relapsed or refractory CD19+/BCMA+ hematologic malignancies, including those with minimal residual disease (MRD). Eligible patients will receive lymphodepletion followed by a single infusion of UCAR-T cells, either post-transplant or without transplantation depending on disease status. The trial assesses overall response and disease control rates, treatment-emergent adverse events, and in vivo behavior of UCAR-T cells.

This single-arm, dose-escalation exploratory trial evaluates the safety and efficacy of Allogeneic CAR-T (UCAR-T) cell therapy in patients with relapsed or refractory CD19+/BCMA+ hematologic malignancies, including those with minimal residual disease (MRD). Eligible patients will receive lymphodepletion followed by a single infusion of UCAR-T cells, either post-transplant or without transplantation depending on disease status.Primary endpoints include treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), pharmacokinetics, and pharmacodynamics of UCAR-T. This study aims to provide initial evidence for the safety and anti-tumor activity of UCAR-T in CD19+/BCMA+ hematologic malignancies.

Inclusion Criteria

1. Voluntary participation with signed informed consent.

2. Pathologically confirmed CD19-positive and/or B-cell maturation antigen (BCMA)-positive hematologic malignancy according to the WHO 2017 classification, including but not limited to multiple myeloma, B-cell acute lymphoblastic leukemia (B-ALL), mature B-cell lymphomas, and plasmablastic lymphoma.

3. Relapsed/refractory disease defined as failure to achieve complete remission after standard therapy, or relapse after an initial response during treatment or follow-up.

4. Measurable disease required:

   1. For B-ALL: persistent minimal residual disease (MRD) positivity despite hematologic remission.
   2. For lymphoma: at least one measurable lesion ≥1.5 cm in longest diameter per IWG revised criteria.
   3. For multiple myeloma: positive immunofixation electrophoresis or presence of extramedullary disease.

5. Age ≥18 years; both sexes eligible.

6. Expected survival ≥12 weeks.

7. Adequate organ function (exceptions for disease-related impairment are at the investigator's discretion):

   1. Total bilirubin <2× upper limit of normal (ULN); serum creatinine <ULN; ALT and AST <3× ULN.
   2. Absolute neutrophil count ≥0.5×10⁹/L; platelets ≥20×10⁹/L (no requirement if marrow involvement is documented).
   3. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
   4. Left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria

1. Known hypersensitivity, allergy, intolerance, or contraindication to CD19/BCMA-UCAR-T or any study drugs (fludarabine, cyclophosphamide, tocilizumab).
2. Genetic syndromes: Fanconi, Kostmann, Shwachman, or any documented bone-marrow failure syndrome.
3. Active or uncontrolled infection requiring IV antibiotics; evidence of severe active infection.
4. NYHA Class III or IV heart failure (unless clearly secondary to the underlying malignancy).
5. Central Nervous System (CNS) disorders unrelated to the primary hematologic malignancy.
6. Prior malignancy except adequately treated carcinoma in situ of skin, cervix, lung, or other non-active tumors.
7. Significant bleeding diathesis (e.g., gastrointestinal (GI) bleeding, coagulopathy, hypersplenism).
8. History of significant cardiac disease within the past 3 months that, in the investigator's judgment, renders the patient unable to tolerate study participation..
9. Pregnancy, lactation, or planned pregnancy within 6 months.
10. Any condition that, in the investigator's opinion, may increase risk or interfere with study results.