Bridging Allogeneic Hematopoietic Stem Cell Transplantation or Not After CD19 CAR - T (S1904) Cell Therapy for r/r B-cell Acute Lymphoblastic Leukemia, a Prospective, Open, Multicenter, Randomized, Control Study (COMPLETE Study)
Traditional salvage chemotherapy has low efficacy and poor long-term prognosis for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Targeted CD19 CAR-T cell immunotherapy is an effective means of treating R/R B-ALL. Several clinical studies have shown that its remission rate for R/R B-ALL can reach 68-93%. However, long-term follow-up found that the remission time after CD19 CAR-T treatment is short and the relapse rate is high. Therefore, how to ensure the long-term survival of R/R B-ALL patients after remission by CAR-T therapy is an urgent problem to be solved. Some studies have shown that timely bridging allo-HSCT after CAR-T treatment can overcome the risk of relapse and further improve the long-term survival of patients. However, there is currently no randomized controlled study on whether to bridge transplantation after CAR-T. The purpose of this study is to evaluate the efficacy and safety of S1904 in the treatment of relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia with or without bridging to allogeneic hematopoietic stem cell transplantation after remission.
• The subject or guardian understands and voluntarily signs the Informed Consent Form (ICF);
• Male or female, aged 12-65 years (including the cutoff value) when signing the informed consent form;
• Expected survival period is not less than 12 weeks;
• ECOG physical performance score is 0-1 when signing the ICF;
• The subject must be diagnosed with relapsed/refractory B-cell acute lymphoblastic leukemia when signing the ICF, and at least one of the following must be met:
∙ Relapse: including relapse within 12 months after the first remission, 2 or more relapses;
‣ Refractory: including primary refractory, failure to achieve remission after at least 2 courses of induction therapy, or failure to achieve remission after at least 1 course of salvage therapy after the first relapse.
• For patients with Philadelphia chromosome-positive ALL (Ph+ ALL), in addition to meeting the above relapse or refractory criteria, they should have failed at least two tyrosine kinase inhibitor (TKI) treatments (except for those with T315I mutations), or be unable to tolerate TKI treatment, or have contraindications to TKI treatment;
• Bone marrow morphology examination at screening showed that the proportion of primitive immature lymphocytes in the bone marrow was \>5%;
• Tumor cells in the bone marrow or peripheral blood were CD19 positive by flow cytometry at screening;
• Major organ functions must meet the following requirements:
∙ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×upper limit of normal (ULN);
‣ Total bilirubin ≤2×ULN;
‣ Serum creatinine clearance of adult subjects ≥60 mL/min (Cockcroft-Gault formula) or creatinine ≤1.5×upper limit of normal (ULN);
‣ Serum creatinine for children: no more than 1.2 mg/dL for 10 to 13 years old, no more than 1.5 mg/dL for males aged 13 to 16 years old, no more than 1.4 mg/dL for females aged 13 years and above, and no more than 1.7 mg/dL for males aged 16 years and above.
⁃ Blood oxygen saturation\>92%;
⁃ Males and females of childbearing age with fertility must agree to use effective contraceptive measures from the signing of the informed consent form until 2 years after the use of the study drug. Females of childbearing age include premenopausal women and women within 2 years after menopause. The blood pregnancy test of females of childbearing age must be negative at the time of screening.