A Phase I Clinical Study on the Safety, Tolerability, and Efficacy of KSV01 Injection in Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia
This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability and preliminary efficacy of KSV01 injection for patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL).
• Voluntary participation and provision of written informed consent by the patient or their legally authorized representative.
• Aged 18 to 80 years (inclusive), any gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Life expectancy \> 3 months.
• Diagnosis of B-cell Acute Lymphoblastic Leukemia (B-ALL) according to the 2016 WHO classification, with relapsed/refractory disease defined by meeting at least one of the following criteria:
‣ Relapse within 12 months of achieving first remission with standard therapy.
⁃ Primary refractory disease: failure to achieve Complete Remission (CR) after two or more cycles of standard chemotherapy.
⁃ Relapsed disease after two or more instances of CR.
⁃ Relapsed or refractory disease following autologous or allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
• Documented CD19-positive leukemia cells in bone marrow or peripheral blood within 1 month prior to screening.
• Morphological disease in the bone marrow (blasts ≥5%).
• For patients with Philadelphia chromosome-positive ALL (Ph+ ALL): must be refractory or intolerant to at least two Tyrosine Kinase Inhibitors (TKIs), including at least one second-generation TKI. Patients with a T315I mutation are exempt from prior TKI salvage therapy.
• Absolute Lymphocyte Count (ALC) ≥ 100/μL.
⁃ Adequate organ function as defined by:
• Hepatic: Alanine aminotransferase (ALT) ≤ 3 × Upper Limit of Normal (ULN); Aspartate aminotransferase (AST) ≤ 3 × ULN; Total bilirubin ≤ 2 × ULN (or ≤ 3 × ULN with a diagnosis of Gilbert's syndrome, with direct bilirubin ≤ 1.5 × ULN).
∙ Renal: Creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 60 mL/min.
∙ Pulmonary: Oxygen saturation (SaO2) ≥ 92% on room air, and no active pulmonary infection.
∙ Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 40% by echocardiography; absence of significant pericardial effusion; no clinically significant electrocardiogram (ECG) abnormalities.
⁃ For women of childbearing potential: negative urine or serum pregnancy test at screening, and agreement to use effective contraception for at least 1 year post-infusion. Male subjects with partners of childbearing potential must agree to use effective barrier contraception for at least 1 year post-infusion.
⁃ For subjects with prior blinatumomab (CD3-CD19 bispecific T-cell engager) therapy: CD19 tumor expression on blasts (from bone marrow or peripheral blood) must be documented after the most recent cycle of blinatumomab. If CD19 expression is quantified, the percentage of CD19-positive blasts must be ≥90%.