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

NCT ID: NCT06985485

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-17
• Study Completion Date: 2027-12-31

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.

Conditions

Acute Lymphoblastic Leukemia; Immunotherapy; Blinatumomab; Inotuzumab Ozogamicin

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Unfit and Fit-Decline B-ALL

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.

Group Type: EXPERIMENTAL

Blinatumomab and Inotuzumab Ozogamicin

Intervention Type: DRUG

Subjects who meet the study criteria during screening will receive induction therapy consisting of low-intensity chemotherapy combined with BiTE 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 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.

Interventions

Blinatumomab and Inotuzumab Ozogamicin

Subjects who meet the study criteria during screening will receive induction therapy consisting of low-intensity chemotherapy combined with BiTE 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 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.

Intervention Type: DRUG

Other Intervention Names

Full-Course Immunotherapy

Eligibility Criteria

Inclusion Criteria

-

(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.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Sheng-Li Xue, MD

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sheng-Li Xue, M.D.

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Soochow University

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sheng-Li Xue, M.D.

Role: CONTACT

slxue@suda.edu.cn

008651267781139

Facility Contacts

Sheng-Li Xue, M.D.

Role: primary

slxue@suda.edu.cn

+8651267781139

Other Identifiers

SZBALL03

Identifier Type: -

Identifier Source: org_study_id