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

Exclusion Criteria

• •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.
• •5. 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%.
• •6. 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.
• •Oxygenation: Oxygen saturation \>92% on room air.
• •7. Non-hematologic toxicities from prior therapies (except disease-related) have resolved to ≤grade 1 before enrollment (excluding alopecia and ≤grade 2 neurotoxicity from chemotherapy).
• •8. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to ZZSW-01 infusion. All fertile male and female participants must agree to use effective contraception during the study and for at least 6 months after the last dose. (Definition of women of childbearing potential and contraceptive methods are detailed in Appendix 1.)
• •9. Ability and willingness to provide written informed consent and to comply with study procedures, follow-up assessments, and treatment.
• •Participants meeting any of the following conditions will be excluded from this study:
• •1. Patients with CNS involvement of B-cell malignancies confirmed by lumbar puncture and/or MRI with CNS-related symptoms.
• •2. Patients with isolated extramedullary relapse of B-ALL.
• •3. Patients with severe hereditary diseases or congenital hematopoietic dysfunction.
• •4. Patients with Burkitt's lymphoma/leukemia or blast phase chronic myeloid leukemia (p210 BCR-ABL+).
• •5. 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.
• •6. 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).
• •7. 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.
• •8. 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).
• •9. 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.
• •10. Autologous stem cell transplantation (ASCT) within 6 weeks prior to ZZSW-01 infusion.
• •11. Any prior allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• •12. Known history of the following diseases:
• •1. . Systemic vasculitis (e.g., Wegener's granulomatosis, polyarteritis nodosa)
• •2. Systemic lupus erythematosus (SLE)
• •3. . Active or uncontrolled autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, autoimmune hemolytic anemia)
• •4. . Primary or secondary immunodeficiency (e.g., HIV infection or severe infectious diseases)
• •13. Evidence of any of the following infections:
• •1. . Chronic or active hepatitis B (HBV) infection (except HBcAb-positive with HBV DNA \<500 IU/mL)
• •2. . Hepatitis C virus (HCV) infection
• •3. . Human immunodeficiency virus (HIV) infection
• •4. . Syphilis infection
• •14. Major surgery within 4 weeks prior to screening, if deemed unsuitable for enrollment by the investigator.
• •15. Concurrent active malignancy. (Patients with prior malignancies cured ≥2 years may be eligible).
• •16. Any of the following cardiac conditions:
• •1. . Left ventricular ejection fraction (LVEF) ≤45% (by echocardiography)
• •2. . NYHA class III or IV congestive heart failure
• •3. . Severe arrhythmia requiring treatment, including QTc ≥450 ms in males or ≥470 ms in females (QTcB=QT/RR1/2)
• •4. . Uncontrolled hypertension (systolic ≥140 mmHg and/or diastolic ≥90 mmHg), pulmonary hypertension, or unstable angina
• •5. . Myocardial infarction, bypass surgery, or stent placement within 12 months prior to dosing
• •6. . Clinically significant valvular heart disease
• •7. . Any other cardiac disease deemed unsuitable by the investigator
• •17. Lymphoma involving the atrium or ventricle.
• •18. Clinical emergencies caused by obstruction or compression from lymphoma masses at screening (e.g., bowel obstruction, vascular compression).
• •19. History of deep vein thrombosis or pulmonary embolism within 6 months prior to screening.
• •20. Hypersensitivity (allergy to ≥2 drugs or foods), or known hypersensitivity to components of the investigational product (compound electrolyte injection, 5% human serum albumin).
• •21. Receipt of live vaccines within 6 weeks prior to screening.
• •22. Uncontrolled active infection at screening (e.g., sepsis, bacteremia, fungemia, viremia).
• •23. Participation in another interventional clinical trial with investigational drugs within 3 months prior to ZZSW-01 infusion, or intent to participate in another clinical trial or receive non-protocol antitumor therapy during the study.
• •24. Any other condition that, in the judgment of the investigator, renders the patient unsuitable for participation.