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

NCT06985485 | Recruiting Phase 2

• 1 other identifier: SZBALL03
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia; Immunotherapy; Blinatumomab; Inotuzumab Ozogamicin

Outcome Measures

Primary Outcomes (1)

• Overall Survival(OS)

  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.

  2 years

Secondary Outcomes (6)

• CR rate(CRR)

  2 years

• Objective Response Rate (ORR)

  2 years

• Event-free survival(EFS)

  2 years

• Relapse-free survival(RFS)

  2 years

• Cumulative incidence of relapse(CIR)

  2 years

Other Outcomes (1)

• immune function

  2 years

Study Arms (1)

Unfit and Fit-Decline B-ALL

EXPERIMENTAL

Newly diagnosed patients who are either: Unfit for intensive chemotherapy, defined as those whose physical conditions (e.g., age, comorbidities, organ dysfunction) preclude tolerance of standard intensive regimens as judged by investigators; or Fit-Declined, defined as patients with good performance status and adequate organ function who decline intensive chemotherapy for subjective reasons(e.g., fear of toxicity, personal preference). Patients with measurable residual disease (MRD) positivity and relapsed or refractory B-ALL following prior chemotherapy (without prior exposure to CD19/CD22-targeted therapies or CAR-T). A low-intensity chemotherapy regimen combined with a sequential treatment regimen of CD19-directed CD3 T-cell engager and inotuzumab ozogamicin is implemented.

Drug: Blinatumomab and Inotuzumab Ozogamicin

Interventions

Blinatumomab and Inotuzumab Ozogamicin DRUG

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.

Also known as: Full-Course Immunotherapy

Unfit and Fit-Decline B-ALL

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients aged ≥60 years, as per NCCN guidelines.
• 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:
• 、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:
• Left ventricular ejection fraction (LVEF) ≥40% by echocardiogram
• Creatinine clearance ≥30 mL/min (by any formula)
• ALT and AST ≤3×ULN, total bilirubin ≤2×ULN (unless attributed to leukemia)
• ≤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.

You may not qualify if:

• Presence of central nervous system (CNS) or other extramedullary disease.
• Concurrent other active malignancies or malignancies requiring treatment.
• 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).
• Use of immunosuppressive agents within 2 weeks prior to signing informed consent, or planned long-term immunosuppressive therapy after enrollment.
• Active cardiac disease (NYHA Class ≥3 as assessed by medical history and physical examination).
• Severe chronic liver disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis \[HBsAb-positive, HCVAb-positive\]).
• 、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.
• 、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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

blinatumomab; Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sheng-Li Xue, M.D.

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheng-Li Xue, M.D.

CONTACT

008651267781139; slxue@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 22, 2025
• Study Start: May 17, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

CN (1)