Sequential Blinatumomab and Inotuzumab Ozogamicin Immunotherapy in Newly Diagnosed B-ALL Patients Unfit/Fit-Declined for Intensive Chemotherapy: A Prospective, Open-Label, Single-Arm Phase II Trial
This trial is a non-blinded, single-center, open-label, single-arm clinical study to investigate a full-course immunotherapy regimen in Unfit or Fit B-cell acute lymphoblastic leukemia (B-ALL) patients who decline chemotherapy (Fit-Decline). The trial aims to explore the efficacy and safety of sequential blinatumomab and inotuzumab ozogamicin therapy. The primary endpoint is overall survival (OS), while secondary endpoints include complete remission rate(CRR)、Objective Response Rate(ORR)、Event-free survival(EFS)、Relapse-free survival(RFS)、Cumulative incidence of relapse(CIR)、Non-relapse mortality(NRM) and safety.
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⁃ (1) Newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients aged ≥60 years, as per the NCCN 2024 guidelines.
⁃ (2) Newly diagnosed B-ALL patients aged ≥15 and \<60 years who are unfit for intensive chemotherapy(Unfit), as per the NCCN 2024 guidelines, and have at least one of the following:
• ECOG score ≥2.
• Severe cardiac comorbidities (e.g., treated congestive heart failure, echocardiogram LVEF ≤50%, unstable angina).
• Severe pulmonary comorbidities (e.g., DLCO ≤65%, FEV1 ≤65%).
• Severe renal comorbidities (e.g., serum creatinine \>2×upper limit of normal (ULN), creatinine clearance \<45 mL/min by any formula).
• Severe hepatic comorbidities (e.g., total bilirubin \>1.5× ULN, AST/ALT/ALP \>3.0× ULN).
• Active infection unresponsive to antimicrobial therapy.
• Cognitive impairment.
• Other comorbidities contraindicating chemotherapy. (3) Newly diagnosed B-ALL patients aged ≥15 years who are physically fit and have normal organ function but refuse intensive chemotherapy for subjective reasons(Fit-Declined) (e.g., fear of toxicity, financial/social/psychological factors, preference for improving quality of life), as per the NCCN 2024 guidelines.
⁃ (4) Adequate major organ function:
• Echocardiogram LVEF ≥40%.
• creatinine clearance ≥30 mL/min by any formula.
• ALT/AST ≤3× ULN, total bilirubin ≤2× ULN (excluding leukemia-related cases).
• ≤Grade 1 dyspnea , oxygen saturation \>91% without supplemental oxygen. (5) Ability to understand and voluntarily sign the informed consent form. (6) Life expectancy ≥3 months.