Full-Course Immunotherapy Consolidation for Unfit or Fit B-ALL Who Decline Chemotherapy

Soochow University

Status and phase: Enrolling; Phase 2

Conditions: Immunotherapy; Blinatumomab; Inotuzumab Ozogamicin; Acute Lymphoblastic Leukemia

Treatments: Drug: Blinatumomab and Inotuzumab Ozogamicin

Study type: Interventional

Funder types: Other

Identifiers

NCT06985485

SZBALL03

Details and patient eligibility

About

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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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:

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 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:

1. Echocardiogram LVEF ≥40%.
2. creatinine clearance ≥30 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. Use of immunosuppressive agents within 2 weeks before signing informed consent, or planned long-term immunosuppressive therapy after enrollment.

5. Active NYHA Class ≥3 heart disease.

6. Severe chronic liver disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis [HBsAb-positive, HCVAb-positive]).

   • Occult or resolved HBV infection (defined as HBcAb-positive but HBsAg-negative) is allowed only if HBV DNA PCR is negative, with mandatory monthly HBV DNA monitoring and prophylactic antiviral therapy.
   • HCV antibody-positive patients are eligible only if HCV RNA PCR is negative.
   • History of severe or persistent VOD/SOS (veno-occlusive disease/sinusoidal obstruction syndrome).

7. Uncontrolled bacterial, fungal, viral, mycoplasma, or other infections as judged by the investigator, including HIV, syphilis, or SARS-CoV-2 infection.

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 disorders or other conditions that may compromise compliance with study procedures, treatment, or monitoring.

13. Pregnant/breastfeeding women, or fertile patients not using contraception.

14. Any other condition deemed unsuitable for study participation by the investigator.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

Unfit and Fit-Decline B-ALL

Experimental group

Description:

Unfit B-ALL patients are defined as whose physical conditions are unable to tolerate standard intensive chemotherapy regimens by investigators. Fit-decline B-ALL patients are defined as who have adequate physiological capacity but declined to undergo intensive chemotherapy. A low-intensity chemotherapy regimen combined with a sequential treatment regimen of blinatumomab and inotuzumab ozogamicin is implemented.

Treatment:

Drug: Blinatumomab and Inotuzumab Ozogamicin