Acute Lymphoblastic Leukemia, Blinatumomab, Immunotherapy, Inotuzumab Ozogamicin
Conditions
Brief summary
This trial is a non-blinded, single-center, open-label, single-arm clinical study to evaluate a full-course immunotherapy regimen in patients with B-cell acute lymphoblastic leukemia (B-ALL). The study population includes newly diagnosed patients who are unfit for or decline intensive chemotherapy, as well as patients with relapsed/refractory disease or with measurable residual disease (MRD) positivity following prior chemotherapy. The trial aims to explore the efficacy and safety of sequential therapy with a CD19-directed CD3 T-cell engager and inotuzumab ozogamicin. 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.
Interventions
DRUGBlinatumomab and Inotuzumab Ozogamicin
Subjects who meet the study criteria during screening will receive induction therapy consisting of low-intensity chemotherapy combined with a CD19-directed CD3 T-cell engager with or without TKIs. Regimen includes dexamethasone, vindesine, followed by blinatumomab dosed by body weight: pts ≥45 kg receive fixed dosing (9 µg/day days 1-7, 28 µg/day days 8-28), pts \<45 kg receive BSA-adjusted dosing (5 µg/m²/day days 1-7, 15 µg/m²/day days 8-28). Philadelphia chromosome-positive ALL pts receive second-generation TKIs, with subsequent switch to third-generation TKIs or asciminib upon resistance. If morphologic remission is not achieved after initial therapy, a salvage cycle with InO will be administered. Post-remission consolidation chemotherapy includes high-dose methotrexate followed by sequential immunotherapy: BiTE (per weight-stratified dosing), then after a 2-week break, InO (0.8 mg/m² on day 1), followed by another 2-week break.This sequence is repeated for 4 cycles.
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients aged ≥60 years, as per NCCN guidelines. 2. Newly diagnosed B-ALL patients aged ≥15 to \<60 years who are unfit for intensive chemotherapy (Unfit), as per NCCN guidelines, meeting at least one of the following criteria: 1、ECOG score ≥2 2、Severe cardiac comorbidities (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction ≤50%, unstable angina) 3、Severe pulmonary comorbidities (e.g., DLCO ≤65%, FEV1 ≤65%) 4、Severe renal comorbidities (e.g., serum creatinine \>2×upper limit of normal (ULN), creatinine clearance \<45 mL/min by any formula) 5、Severe hepatic comorbidities (e.g., total bilirubin \>1.5×ULN, AST/ALT/ALP \>3×ULN) 6、Active infection refractory to antimicrobial therapy 7、Documented cognitive impairment 8、Other comorbidities contraindicating intensive chemotherapy (3) Newly diagnosed B-ALL patients aged ≥15 to \<60 years with good performance status and adequate organ function who decline intensive chemotherapy for subjective reasons (Fit-Declined), as per NCCN guidelines (e.g., fear of toxicity, financial/social/psychological factors, preference for quality of life). (4) Patients aged ≥15 years with relapsed/refractory B-ALL or MRD positivity after prior chemotherapy (5) All patients must meet the following organ function requirements: 1. Left ventricular ejection fraction (LVEF) ≥40% by echocardiogram 2. Creatinine clearance ≥30 mL/min (by any formula) 3. ALT and AST ≤3×ULN, total bilirubin ≤2×ULN (unless attributed to leukemia) 4. ≤Grade 1 dyspnea and oxygen saturation \>91% without supplemental oxygen (6) Ability to understand and voluntarily sign the informed consent form. (7) Life expectancy ≥3 months.
Exclusion criteria
1. Presence of central nervous system (CNS) or other extramedullary disease. 2. Concurrent other active malignancies or malignancies requiring treatment. 3. Prior exposure to CD19- or CD22-targeted therapies (including but not limited to CD19-directed CD3 T-cell engager, inotuzumab ozogamicin, CD19 or/and CD22 CAR-T). 4. Use of immunosuppressive agents within 2 weeks prior to signing informed consent, or planned long-term immunosuppressive therapy after enrollment. 5. Active cardiac disease (NYHA Class ≥3 as assessed by medical history and physical examination). 6. Severe chronic liver disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis \[HBsAb-positive, HCVAb-positive\]). 1、Patients with occult or prior HBV infection (defined as HBcAb-positive, HBsAg-negative) are eligible only if HBV DNA PCR is negative, and require monthly HBV DNA monitoring with prophylactic antiviral therapy. 2、HCV antibody-positive patients are eligible only if HCV RNA PCR is negative. 3、History of confirmed severe or persistent veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). (7) Bacterial, fungal, viral, mycoplasma, or other infections that are uncontrolled as judged by the investigator; HIV, syphilis, or SARS-CoV-2 infection. (8) Past or current CNS disorders, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease. (9) Primary immunodeficiency or active autoimmune disease. (10) History of severe immediate hypersensitivity to any study drugs. (11) Receipt of live vaccine within 6 weeks prior to screening. (12) Psychiatric disorders or other conditions that may compromise compliance with study requirements, treatment, or monitoring. (13) Pregnant or breastfeeding women, or fertile patients unwilling to use contraception. (14) Any other condition deemed unsuitable for study participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival(OS) | 2 years | It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR rate(CRR) | 2 years | CR rate (CR defined as bone marrow blasts \< 5% and no Auer rods, absence of extramedullary disease, ANC ≥ 1.0 × 109/L \[1000/µL\], platelet count ≥ 100 × 109/L \[100,000/µL\], and independence of RBC transfusions). |
| Objective Response Rate (ORR) | 2 years | Objective response rate (ORR) is defined as the rate of CR, CRi (including complete remission with incomplete platelet recovery \[CRp\], PR, and MLFS. |
| Event-free survival(EFS) | 2 years | Event-free survival (EFS) is defined as the time from the start of treatment until treatment failure, relapse from remission, or death from any cause, whichever occurs first. |
| Relapse-free survival(RFS) | 2 years | Relapse-free survival(RFS) is the time from achievement of complete remission (CR) to the first documented relapse or death from any cause. Patients who die without evidence of relapse are typically censored at the last disease-free assessment. |
| Cumulative incidence of relapse(CIR) | 2 years | It is measured the date from complete remission to hematological relapse or molecular relapse was recorded. Patients who had no relapse at the last follow-up were considered as censored data, and non-relapse death was regarded as a competing risk event. |
| Non-relapse mortality(NRM) | 2 years | It is measured the probability of death attributable to treatment-related complications or comorbidities, excluding disease relapse/progression. |
Countries
China
Contacts
CONTACTSheng-Li Xue, M.D.
PRINCIPAL_INVESTIGATORSheng-Li Xue, M.D.
The First Affiliated Hospital of Soochow University
Outcome results
None listed