A Clinical Study of Allogeneic CD19/BCMA CAR-T Cells for the Treatment of R/R B-cell Malignant Tumors

Official title

An Exploratory Clinical Study on the Safety and Efficacy of Allogeneic CD19/BCMA CAR-T Cell Treatment for Relapsed/ Refractory B-cell or Plasma Cell-derived Malignant Tumors

Overview

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.

Interventions

• Drug RN1101 injection
  RN1101 injection is an allogenic CAR-T targeted CD19 and BCMA. A single infusion of CAR-T cells will be administered intravenously.

Primary outcome measures

• Incidence and severity of adverse events after RN1101 infusion [Time frame: up to 24 weeks after RN1101 infusion]

Secondary outcome measures (6)

• Percentage of MRD negative patients after RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]
• ORR (PR, VGPR, CR and sCR) of patients receive RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]
• Progression free survival after RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]
• CAR copies and cell count of CAR-T in blood and bone marrow (if available) after RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]
• Duration of response after RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]
• Overall survival after RN1101 treatment [Time frame: 12 weeks, 24 weeks after RN1101 infusion]

Eligibility criteria

Inclusion criteria

• Willingness to participate in the trial and provision of signed informed consent.
• 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.
• 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.
• Patients with B-cell acute lymphoblastic leukemia (ALL) who have achieved hematologic remission but have persistent minimal residual disease (MRD).
• 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.
• 18 Years and older, regardless of gender.
• An expected survival of ≥12 weeks.
• 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.
• 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.
• ECOG performance status of 0 - 2.
• Left ventricular ejection fraction (LVEF) ≥50% and no pericardial effusion.
• At least 2 weeks have passed since the last treatment (radiotherapy, chemotherapy, monoclonal antibody therapy, or other treatments).

Exclusion criteria

• 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.
• Recurrence after allogeneic hematopoietic stem cell transplantation with active graft - versus - host disease (GVHD) requiring steroid or immunosuppressive therapy.
• Severe active infection.
• Acquired or congenital immunodeficiency.
• New York Heart Association (NYHA) Class Ⅲ or Ⅳ heart failure.
• History of epilepsy or other central nervous system diseases.
• Lymphoma with extranodal involvement of the brain, lungs, or gastrointestinal tract.
• Other primary cancers, except:

• Non-melanoma skin cancer (e.g., basal cell carcinoma) cured by resection.
• Carcinoma in situ (e.g., cervical, bladder, or breast cancer) cured.
• Systemic high-dose steroids within 2 weeks before treatment.
• Pregnant, breastfeeding, or plans to become pregnant within 6 months.
• Participation in another clinical trial within the past month.
• Any situation the investigator deems may raise risks or interfere with trial results.

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 · 1 center

• Affiliated Hospital of Jiangsu University — Zhenjiang

Identifiers

NCT: NCT06976437 · RunNing

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗