Full-course immunotherapy for B‑cell acute lymphoblastic leukemia patients who are unfit for or decline chemotherapy

A Phase II Trial of Sequential Blinatumomab and Inotuzumab Ozogamicin in Newly Diagnosed (Unfit/Fit-Declined), Relapsed/Refractory, and MRD-Positive B-ALL

This study will try a full course of sequential immunotherapy with blinatumomab followed by inotuzumab ozogamicin for people with B‑cell ALL who are older, unfit for, have relapsed/refractory disease, or who decline intensive chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 15 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: inotuzumab, CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT06985485 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center, open-label, single-arm study gives sequential CD19-directed CD3 T-cell engager therapy (blinatumomab) followed by inotuzumab ozogamicin to patients with B‑cell ALL who are newly diagnosed but unfit for or who decline intensive chemotherapy, as well as to those with relapsed/refractory disease or MRD positivity. The trial is non-blinded and enrolls patients at The First Affiliated Hospital of Soochow University. The primary endpoint is overall survival, and secondary endpoints include complete remission rate, objective response rate, event-free survival, relapse-free survival, cumulative incidence of relapse, non-relapse mortality, and safety. Safety monitoring and response assessments will follow standard hematologic oncology practice with serial bone marrow evaluations and clinical follow-up.

Who should consider this trial

Good fit: Ideal candidates are patients with B‑cell ALL who are aged ≥60, or aged 15–<60 and deemed unfit for intensive chemotherapy, as well as patients with relapsed/refractory disease or MRD positivity after prior chemotherapy.

Not a fit: Patients with CD19-negative disease, severe organ dysfunction or active uncontrolled infections that preclude immunotherapy, or those who are candidates for and tolerate standard intensive chemotherapy may not benefit from this chemo-only approach.

Why it matters

Potential benefit: If successful, this approach could offer a chemo-free consolidation option that increases remission rates and overall survival for patients who cannot or will not tolerate intensive chemotherapy.

How similar studies have performed: Both blinatumomab and inotuzumab ozogamicin have shown benefit individually in relapsed/refractory and MRD-positive B‑ALL, but using a full-course sequential immunotherapy regimen as the primary consolidation instead of chemotherapy is relatively novel and less tested.

Eligibility criteria

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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Principal investigator: Sheng-Li Xue, M.D. — The First Affiliated Hospital of Soochow University
• Study coordinator: Sheng-Li Xue, M.D.

Conditions Acute Lymphoblastic Leukemia; Immunotherapy; Blinatumomab; Inotuzumab Ozogamicin