Effectiveness and Safety of InO±DLI for Relapsed B-ALL/LBL After Allo-HSCT

NCT ID: NCT06861348

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2027-04-30

Brief Summary

B cell acute lymphoblastic leukemia (B-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of B-lineage precursor cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curable therapy for ALL, especially for high-risk ALL patients. However, post-HSCT recurrence is the primary cause of transplant failure and salvage treatment option for this patient population are very limited. Current data showed that the CR rate and overall survival (OS) in adults with ALL who relapse after transplantation are as low as 30% and 25%, respectively, and the prognosis is extremely dismal. Some researchers have successfully salvage treated relapsed B-ALL patients after transplantation with donor lymphocyte infusions (DLI), but the response rate of DLI alone is usually less than 10%, with increased risk of Graft-Versus-Host Disease (GvHD). In the immunotherapy era, the introduction of immuno-designed therapies like bispecific antibody constructs, antibody conjugates, as well as chimeric antigen receptor T cell (CAR-T) therapy, have immensely broadened the treatment landscape of relapsed or refractory (r/r) B-ALL. Inotuzumab ozogamicin (InO) is a CD22-targeted monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. Based on the pivotal Phase III INO-VATE clinical trial published in N Engl J Med in 2016, compared to standard chemotherapy, 73% (64/88) of r/r B-ALL patients treated with InO achieved CR/CRi in the first cycle. Superior CR duration, OS and relapse free survival (RFS) was also observed in the InO group. Subgroup analysis showed that the treatment benefits were consistent for patients who relapsed after allo-HSCT. Moreover, a single-center retrospective study attempted to salvage treat relapsed B-ALL patients after transplantation with combined InO and DLI, results showed that six out of eight patients achieved CR after the first InO course and 75% of patients obtained MRD negativity after the second course, which is quite satisfactory. Therefore, we designed a Phase II clinical study of InO combined with or without DLI in patients with recurrent acute B-ALL/LBL after allo-HSCT, with expectation to increase CR rate and improve long-term survival.

Conditions

Leukemia, Lymphocytic, Acute

Study Design

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

Study Groups

Ino±DLI regimen

1\. InO induction：the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 2.InO consolidation：If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8, d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 3. DLI: CD3 positive cells 1x10\^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD.

Group Type: EXPERIMENTAL

Inotuzumab Ozogamicin±Donor Lymphocyte Infusion

Intervention Type: DRUG

Participants will receive Ino±DLI regimen:

• ① InO induction dose: the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
• ② If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8，d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
• ③DLI dose: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD;
• Lumbar puncture: cytarabine 50mg+dexamethasone 5mg+methotrexate 10mg, intrathecal injection, once a month after remission, a total of 4-6 courses of treatment.

Interventions

Inotuzumab Ozogamicin±Donor Lymphocyte Infusion

Participants will receive Ino±DLI regimen:

• ① InO induction dose: the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
• ② If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8，d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
• ③DLI dose: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD;
• Lumbar puncture: cytarabine 50mg+dexamethasone 5mg+methotrexate 10mg, intrathecal injection, once a month after remission, a total of 4-6 courses of treatment.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Aged 14-65 years, male or female;

2. Participants with CD22 positive B-ALL/LBL who relapsed after allo-HSCT from a related or unrelated donor (regardless of CD22 expression);

3. ECOG physical status score 0~3, Karnofsky score ≥70;

4. No active grade III/IV graft-versus-host disease (GvHD) or any active liver GvHD, no history of venous occlusive disease (VOD); No active GvHD and no previous history of VOD;

5. Creatinine clearance rate≥50 mL/min (estimate by Cockcroft-Gault Equation);

6. Liver function: alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 3×upper limit of normal (ULN), and total bilirubin ≤ 2×ULN;

7. Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiography;

8. Estimated life expectancy >3 months;

9. Participants voluntarily participate in clinical trial; Understand and know this study, sign an informed consent form, and be willing to follow all experimental procedures.

Exclusion Criteria

1. Allergic or with a history of serious adverse reactions to drugs or drugs with similar chemical structure in this study;

2. Women who are pregnant or breastfeeding, as well as those who are unwilling to take effective contraceptive measures;

3. Severe cardiac dysfunction: left ventricular ejection fraction (LVEF) <60%; Or severe arrhythmia: a history of a clinically significant corrected interval (QTc) prolongation (male >450ms; female>470 ms), ventricular tachycardia, atrial fibrillation, second degree atrioventricular block; myocardial infarction and coronary heart disease with clinical symptoms requiring medical treatment within one year before enrollment;

4. Severe pulmonary disorders (obstructive or restrictive ventilation disorder);

5. Severe liver function impairment: ALT, AST, or TBIL is more than 3 times higher than the upper limit of normal value (ULN);

6. Severe renal impairment: serum Cr is more than 2 times higher than the upper limit of normal (ULN); Or 24-hour urinary creatinine clearance <50ml/min;

7. Participants with active infection or active bleeding who were deemed intolerance to InO treatment by the investigators;

8. A history of new thrombosis, embolism, cerebral hemorrhage or other diseases within one year before enrollment;

9. Participants suffer from known or other mental disorders that investigators are unable to obtain informed consent and may interfere with their ability to comply with research requirements;

10. A history of major organ surgery within the past six weeks;

11. Drug abuse or chronic alcohol abuse that may affect the study results;

12. Participants with a history of organ transplantation other than HSCT (except BMT);

13. Other situations identified by the investigator as unsuitable to participate in the study.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Yi Luo

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yi Luo, M.D.

Role: PRINCIPAL_INVESTIGATOR

First Affilaated Hospital of Medical School of Zhejiang University

Locations

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, , China

Countries

China

Central Contacts

Yi Luo, M.D.

Role: CONTACT

luoyijr@zju.edu.com

+8613666609126

Honghu Li, M.D.

Role: CONTACT

21518022@zju.edu.cn

+8618158514785

Facility Contacts

Yi Luo, M.D.

Role: primary

luoyijr@zju.edu.com

86-13666609126

Honghu Li, M.D.

Role: backup

21518022@zju.edu.cn

+8618158514785

Other Identifiers

IIT20240086C-X1

Identifier Type: -

Identifier Source: org_study_id