Clinical trial NCT06985485: Full-Course Immunotherapy Consolidation for Unfit or Fit B-ALL Who Decline Chemotherapy
Official title: Sequential Blinatumomab and Inotuzumab Ozogamicin in Unfit and Fit Declined B-ALL Patients: A Single-Arm Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Immunotherapy
Blinatumomab
Inotuzumab Ozogamicin
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2025-05-22
Enrollment: 30
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

-

(1) Newly diagnosed Ph- B-ALL or Ph+ B-ALL patients aged ≥60 years, as per the NCCN 2024 guidelines.

(2) Newly diagnosed Ph- B-ALL or Ph+ B-ALL patients aged ≥15 and \<60 years who are unfit for intensive chemotherapy, as per the NCCN 2024 guidelines, and have at least one of the following:

1. ECOG score ≥2.
2. Severe cardiac comorbidities (e.g., treated congestive heart failure, echocardiogram LVEF ≤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 \>3.0× ULN).
6. Active infection unresponsive to antimicrobial therapy.
7. Cognitive impairment.
8. Other comorbidities contraindicating chemotherapy. (3) Newly diagnosed Ph- B-ALL or Ph+ B-ALL patients aged ≥18 years who are physically fit and have normal organ function but refuse intensive chemotherapy for subjective reasons (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:

1. Echocardiogram LVEF ≥50%.
2. Serum creatinine ≤2× ULN or creatinine clearance ≥45 mL/min by any formula.
3. ALT/AST ≤3× ULN, total bilirubin ≤2× ULN (excluding leukemia-related cases).
4. ≤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.

Exclusion Criteria:

1. Presence of extramedullary disease.
2. Concurrent other active or treatment-requiring malignancies.
3. Prior CD19/CD22-targeted therapy.
4. Immunosuppressants or steroids used within 2 weeks before consent, or planned long-term use post-consent.
5. Active NYHA Class ≥3 heart disease.
6. Active hepatitis; history of HBV (HBsAg+) or HCV (HCV antibody+). Occult/precore HBV (HBcAb+, HBsAg-) allowed if HBV DNA PCR-negative, with monthly monitoring. HCV antibody+ patients can enroll if HCV RNA PCR-negative.
7. Uncontrolled infections, including HIV, syphilis, or COVID-19.
8. Past/current CNS disorders (e.g., seizures, cerebrovascular events, dementia, cerebellar disease, CNS autoimmune diseases).
9. Primary immunodeficiency or active autoimmune disease.
10. History of severe immediate hypersensitivity to any study drugs.
11. Live vaccine receipt within 6 weeks before screening.
12. Psychiatric conditions or inability to comply with study requirements.
13. Pregnant/breastfeeding women, or fertile patients not using contraception.
14. Investigator-assessed unsuitability for the study.

Primary outcomes:
measure: Overall Survival(OS)
timeFrame: 2 years
Secondary outcomes:
measure: CR rate(CRR)
timeFrame: 2 years
measure: Objective Response Rate (ORR)
timeFrame: 2 years
measure: Event-free survival(EFS)
timeFrame: 2 years
measure: Relapse-free survival(RFS)
timeFrame: 2 years
measure: Cumulative incidence of relapse(CIR)
timeFrame: 2 years
measure: Non-relapse mortality(NRM)
timeFrame: 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Sheng-Li Xue, M.D.
role: PRINCIPAL_INVESTIGATOR
References: