Early Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of SYNCAR-100 in the Treatment of CD19-Positive Relapsed or Refractory Acute B-Lymphoblastic Leukemia (R/R B-ALL)
The purpose of this study is to assess the safety, tolerability, and preliminary efficacy of SYNCAR-100 in patients with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Participants who have signed the informed consent form will undergo screening against the inclusion and exclusion criteria. Eligible participants will receive study drug administration once weekly for a total of four doses, followed by a 1-year safety and efficacy follow-up observation period. After the completion of the study, long-term follow-up may be required for participants to monitor their health and survival status until 15 years post-treatment, or until the occurrence of patient death, loss to follow-up, or withdrawal of consent.
• 1.Aged 18 to 75 years (inclusive), of any gender.
• 2.Karnofsky Performance Status score ≥ 70.
• 3.Estimated life expectancy ≥ 12 weeks.
• 4.Positive CD19 expression on tumor cells confirmed by flow cytometry in bone marrow or peripheral blood.
• 5.Confirmed diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) by bone marrow examination, and meeting one of the following criteria:
• ① Refractory B-ALL: Failure to achieve complete remission (CR) after 2 courses of standard induction chemotherapy, or failure to achieve CR after first-line/multiline salvage chemotherapy.
• ② Relapsed B-ALL: Relapse within 12 months after the first remission, or relapse after first-line/multiline salvage chemotherapy.
• ③Relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT).
• ④ For Philadelphia chromosome-positive (Ph+) patients: At least 2 lines of tyrosine kinase inhibitor (TKI) therapy have failed, or the patient is intolerant to TKI therapy, or the patient harbors the T315I mutation and is resistant to TKIs.
• 6.Proportion of blasts and immature lymphocytes in bone marrow \> 5% confirmed by bone marrow morphologic examination.
• 7.No prior hematopoietic stem cell transplantation (HSCT) within 6 months before enrollment.
• 8.Adequate organ function reserve, as defined by all of the following:
• ① Creatinine clearance (calculated by the Cockcroft-Gault formula) \> 60 mL/min: Male: Creatinine Clearance = \[(140 - Age) × Body Weight (kg)\] / \[0.818 × Serum Creatinine (μmol/L)\] Female: Creatinine Clearance = \[(140 - Age) × Body Weight (kg) × 0.85\] / \[0.818 × Serum Creatinine (μmol/L)\]
• ② Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 times the upper limit of normal (ULN) ; for patients with hepatic metastasis, AST and ALT ≤ 5 times the upper limit of normal (ULN) .
• ③Serum total bilirubin \< 1.5 times the upper limit of normal (ULN) ; for patients with Gilbert's syndrome, total bilirubin ≤ 3 times the upper limit of normal (ULN) .
• ④ Absolute lymphocyte count (ALC) ≥ 0.1 × 10\^9/L.
• ⑤Left ventricular ejection fraction (LVEF) \> 50% confirmed by echocardiography, with no clinically significant pericardial effusion on echocardiography.
• ⑥ No clinically significant pleural effusion.
• ⑦ Baseline peripheral oxygen saturation (measured at the fingertip) \> 92% while breathing room air.
• 9.For women of childbearing potential: Non-lactating; negative result of highly sensitive serum or urine pregnancy test during screening. All women of childbearing potential must use medically accepted contraceptive methods (e.g., intrauterine device, oral contraceptives) throughout the treatment period and for 2 years after the first treatment. For males of childbearing potential: Sperm donation is prohibited during the same period.
• 10.Ability to communicate effectively with investigators; willingness and ability to comply with the study protocol, complete all study-related procedures as required, and provide written informed consent (signed voluntarily by the patient or their legal guardian).