CAR 70-BCMA CAR-T Cells for the Treatment of Relapsed or Refractory Plasma Cell Neoplasms

Clinical Study on the Safety and Efficacy of CAR 70-BCMA Dual-Target CAR-T Therapy for Relapsed or Refractory Plasma Cell Neoplasms

This is a single arm study to evaluate the safety and efficacy of CAR70-BCMA dual-target CAR-T cell therapy for relapsed and refractory plasma cell neoplasms.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory Plasma Cell Neoplasms
• Intervention / Treatment: Genetic: CAR 70-BCMA CAR-T; Drug: Fludarabine and Cyclophosphamide

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Hai Yi; Phone Number: 13699418229; Email: yihaimail@163.com

Study Locations

• China
  • Chengdu
    • Chengdu, Chengdu, China
      • General Hospital of Western Theater Command of PLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject or their legally authorized representative has provided written informed consent and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.

2. Diagnosis of relapsed or refractory plasma cell neoplasms, defined as follows:

   1. Clonal plasma cells positive for BCMA and/or CD70 expression as determined by flow cytometry or immunohistochemistry;
   2. Patients with multiple myeloma, plasmacytoma, or plasma cell leukemia who have received at least three prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody, and whose best response was less than partial response (PR) or who experienced disease progression after achieving at least PR;
   3. Patients with systemic light chain amyloidosis who have received at least two prior lines of therapy, including an anti-CD38 monoclonal antibody and either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD), and whose best response was less than partial response (PR) or who experienced disease progression after achieving at least PR.
3. Aged 18 to 75 years (inclusive), male or female.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Life expectancy greater than 3 months from the date of informed consent.
6. Hemoglobin (HGB) ≥ 60 g/L (transfusion permitted).

7. Adequate hepatic, renal, cardiac, and pulmonary function meeting the following criteria:

   1. Creatinine ≤ 2 × upper limit of normal (ULN);
   2. Left ventricular ejection fraction (LVEF) ≥ 50%;
   3. Oxygen saturation > 90%;
   4. Total bilirubin ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
8. The subject agrees to use contraceptive measures from the time of signing the informed consent form until 1 year after CAR-T cell infusion.

Exclusion Criteria:

• 1. Severe cardiac dysfunction with left ventricular ejection fraction (LVEF) < 50%; 2. History of severe pulmonary function impairment; 3. Concurrent progressive malignancy; 4. Concurrent severe infection that cannot be adequately controlled; 5. Concurrent severe autoimmune disease or congenital immunodeficiency; 6. Active hepatitis, defined as hepatitis B virus deoxyribonucleic acid (HBV-DNA) or hepatitis C virus ribonucleic acid (HCV-RNA) above the lower limit of detection; 7. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection; 8. History of severe allergic reaction to biological products (including antibiotics); 9. Patients who have undergone allogeneic hematopoietic stem cell transplantation and still have acute graft-versus-host disease (GVHD) one month after discontinuation of immunosuppressive agents; 10. Presence of any other serious physical or mental illness, or laboratory abnormality that may increase the risk of study participation, interfere with the interpretation of study results, or render the patient unsuitable for study enrollment in the opinion of the investigator; 11. Female patients of childbearing potential who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: This is a single arm treatment of CAR 70-BCMA CAR-T cell; CAR 70-BCMA CAR-T Therapy. Investigational product: CAR 70-BCMA CAR-T. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of CAR 70-BCMA CAR-T cells.

Genetic: CAR 70-BCMA CAR-T; Each subject will receive a single infusion of BCMA-CD70-CAR-T cells. A classic "3+3" dose escalation design will be employed.; Drug: Fludarabine and Cyclophosphamide; Drug: Fludarabine Fludarabine will be administered intravenously (IV) at a dose of 30 mg/m²/day for 3 consecutive days prior to the infusion of 70-BCMA-CAR-T cells. Drug: Cyclophosphamide Cyclophosphamide will be administered intravenously (IV) at a dose of 300 mg/m²/day for 3 consecutive days prior to the infusion of 70-BCMA-CAR-T cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of CAR70-BCMA dual-target chimeric antigen receptor T-cell therapy in patients with relapsed or refractory plasma cell neoplasms expressing CD70 and/or BCMA based on the incidence of treatment-emergent adverse events (AEs).	Incidence of treatment-emergent adverse events (AEs) Description: Number and severity of AEs graded according to CTCAE v5.0, including cytokine release syndrome (CRS) graded according to ASTCT criteria and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASBMT criteria	Up to 3 years
To evaluate the safety of CAR70-BCMA CAR-T cells in the treatment of relapsed or refractory plasma cell neoplasms positive for CD70/BCMA based on the determination of the maximum tolerated dose (MTD).		MTD will be determined based on dose-limiting toxicities (DLTs) observed during the first 28 days after the start of study treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of CAR70-BCMA CAR-T cells in the treatment of relapsed or refractory plasma cell neoplasms positive for CD70/BCMA based on the objective response rate (ORR).	Objective response rate (ORR) Description: For multiple myeloma (plasma cell neoplasms, plasma cell leukemia), the efficacy evaluation criteria refer to the Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma (2024 Revision). ORR includes the proportion of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR).	Within 3 months following infusion of CAR70-BCMA CAR-T cells

Other Outcome Measures

Outcome Measure	Time Frame
To explore the kinetics and clonal evolution of CAR70-BCMA CAR-T cells based on pharmacokinetics (assessing the persistence of CAR-T cells by measuring CAR-T cell counts in peripheral blood).	Up to 12 months after CAR-T treatment

Collaborators and Investigators

• Sponsor: The General Hospital of Western Theater Command

Study record dates

Study Major Dates

• Study Start (Estimated): April 3, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; BCMA; CD70; Relapsed and Refractory Plasma Cell Neoplasms.
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Pathological Conditions, Signs and Symptoms; Recurrence; Neoplasms, Plasma Cell; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: CAR 70-BCMA-YHWX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No