Safety and Efficacy of ZZSW-01 in Relapsed/Refractory B-cell Malignancies

NCT07240974 | Recruiting Early Phase 1

• 1 other identifier: EVB20250627
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, open-label, dose-escalation, early-phase 1 study to evaluate the safety, tolerability and preliminary efficacy of ZZSW-01 injection in patients with relapsed/refractory B-cell malignancies.

Conditions

Relapsed/Refractory B-cell Malignancies

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events

  All adverse events (AEs), including severe adverse events (SAEs) and clinically significant laboratory abnormalities, will be recorded and graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

  Up to 28 days post-infusion

• Incidence of Dose-Limiting Toxicities (DLTs)

  Dose-limiting toxicities (DLTs) will be specifically identified, recorded, and monitored during the designated DLT observation period.

  Up to 28 days post-infusion

• Incidence and Severity of Cytokine Release Syndrome (CRS)

  Cytokine release syndrome (CRS) events will be identified and graded for severity according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.

  Up to 28 days post-infusion

• Incidence and Severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

  Immune effector cell-associated neurotoxicity syndrome (ICANS) will be assessed using the Immune Effector Cell-Associated Encephalopathy (ICE) score and subsequently graded for severity according to the ASTCT consensus grading.

  Up to 28 days post-infusion

Secondary Outcomes (14)

• Complete Response (CR) Rate of administering ZZSW-01 in the treatment of relapsed/refractory of B-cell malignancies.

  From ZZSW-01 infusion to the end of the treatment at 96 weeks

• Partial Response (PR) Rate of administering ZZSW-01 in the treatment of relapsed/refractory of B-cell malignancies.

  From ZZSW-01 infusion to the end of the treatment at 96 weeks

• Stable Disease (SD) Rate of administering ZZSW-01 in the treatment of relapsed/refractory of B-cell malignancies.

  From ZZSW-01 infusion to the end of the treatment at 96 weeks.

• Progressive Disease (PD) Rate of administering ZZSW-01 in the treatment of relapsed/refractory of B-cell malignancies.

  From ZZSW-01 infusion to the end of the treatment at 96 weeks.

• Objective response rate (ORR) of administering ZZSW-01 in the treatment of relapsed/refractory of B-cell malignancies.

  From ZZSW-01 infusion to the end of the treatment at 96 weeks

Study Arms (1)

ZZSW-01

EXPERIMENTAL

ZZSW-01 is an extracellular vesicle that carries functional CD19 CAR mRNA, which can be administered intravenously to generate CAR-T cells in vivo.

Drug: ZZSW-01 injection

Interventions

ZZSW-01 injection DRUG

ZZSW-01 is an extracellular vesicle that carries functional CD19 CAR mRNA, which can be administered intravenously to generate CAR-T cells in vivo.

Also known as: CAR-EVs

ZZSW-01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, no restriction on sex.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0-2.
• Expected survival ≥3 months.
• Histologically or cytologically confirmed CD19-positive relapsed or refractory B-cell malignancies according to the WHO classification of lymphoid neoplasms, including:
• Relapsed/refractory B-NHL: patients who have failed at least two prior lines of therapy, are intolerant to the toxicity of second-line regimens, or are not eligible for autologous stem cell transplantation, including but not limited to diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL/high-grade B-cell lymphoma with MYC and BCL2 rearrangements, high-grade B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, mantle cell lymphoma, grade 3b follicular lymphoma, and transformed large B-cell lymphoma from indolent B-NHL.
• Relapsed/refractory precursor B-ALL: patients who relapse after achieving CR following second-line therapy, or who fail to achieve CR/CRi after completion of second-line therapy.
• For relapsed/refractory B-NHL: at least one measurable lesion as assessed by the investigator (e.g., lymph node with long axis \>15 mm, or extranodal lesion with long axis \>10 mm).
• For relapsed/refractory precursor B-ALL: baseline bone marrow blasts ≥5%.
• Adequate organ function as defined below (no administration of blood components or hematopoietic growth factors within 14 days prior to first dosing):
• Hematology:
• Relapsed/refractory B-NHL: ANC ≥1.5×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥70 g/L, absolute CD8+ T-cell count ≥0.3×10\^9/L; if bone marrow involvement is present: ANC ≥1.0×10\^9/L, platelets ≥50×10\^9/L, hemoglobin ≥70 g/L.
• Relapsed/refractory precursor B-ALL: ANC ≥1.0×10\^9/L (G-CSF support permitted), platelets ≥50×10\^9/L (no platelet transfusion within 7 days), hemoglobin ≥80 g/L (no RBC transfusion within 7 days); if bone marrow involvement or not in remission: ANC ≥0.5×10\^9/L (G-CSF support permitted), platelets ≥30×10\^9/L (no platelet transfusion within 7 days), hemoglobin ≥70 g/L (no RBC transfusion within 7 days). Additionally, absolute CD8+ T-cell count ≥0.2×10\^9/L and CD19+ B-cell percentage ≤5%.
• Liver function: TBIL ≤1.5×ULN; ALT and AST ≤2.5×ULN (≤5×ULN if liver metastases are present).
• Renal function: Serum creatinine ≤1.5×ULN (if \>1.5×ULN, creatinine clearance must be ≥50 mL/min).
• Coagulation: INR ≤1.5×ULN and APTT ≤1.5×ULN; patients on anticoagulation may be included if INR ≤2.5×ULN.

You may not qualify if:

• Participants meeting any of the following conditions will be excluded from this study:
• Patients with CNS involvement of B-cell malignancies confirmed by lumbar puncture and/or MRI with CNS-related symptoms.
• Patients with isolated extramedullary relapse of B-ALL.
• Patients with severe hereditary diseases or congenital hematopoietic dysfunction.
• Patients with Burkitt's lymphoma/leukemia or blast phase chronic myeloid leukemia (p210 BCR-ABL+).
• Current or past history of central nervous system disorders, including: seizures, ischemic/hemorrhagic cerebrovascular disease, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychiatric illness, or any autoimmune disease involving the CNS.
• Receipt of chemotherapy within 2 weeks prior to ZZSW-01 infusion (except intrathecal chemotherapy for prevention of CNS leukemia, which must be stopped ≥1 week prior to infusion).
• Prior systemic immune checkpoint inhibitor therapy (e.g., anti-PD-1/PD-L1 mAbs) within fewer than 3 half-lives before ZZSW-01 infusion; or other systemic antitumor therapy within fewer than 2 weeks or 5 half-lives (whichever is shorter) before infusion.
• Use of systemic therapeutic corticosteroids within 72 hours prior to ZZSW-01 infusion (physiologic replacement doses are allowed, e.g., prednisone \<10 mg/day or equivalent).
• Receipt of targeted therapies or antibody drugs (including BiTEs, antibody-drug conjugates) within 2 weeks, or cytotoxic therapy within 1 week prior to ZZSW-01 infusion.
• Autologous stem cell transplantation (ASCT) within 6 weeks prior to ZZSW-01 infusion.
• Any prior allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Known history of the following diseases:
• Systemic vasculitis (e.g., Wegener's granulomatosis, polyarteritis nodosa)
• Systemic lupus erythematosus (SLE)

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, 430022, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Heng Mei, Ph.D&M.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, Ph.D&M.D

CONTACT

027-8572600; hmei@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: November 21, 2025
• Study Start: October 28, 2025
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2028
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)