Inotuzumab Ozogamicin in the Treatment of MRD+ After HSCT of ALL

Study Overview
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Brief Summary
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As part of postremission consolidative therapy, the decision to proceed with hematopoietic stem cell transplantation is a recommendable regimen in ALL therapy. However, The recurrence rate is high after transplantation. Minimal Residual Disease (MRD) is an important factor affecting the effect of HSCT. The hematologic recurrence rate of MRD-positive patients with adult ALL is high. MRD- is associated with better prognosis. Therefore, maintaining MRD- after transplantation is necessary for long-term survival. The purpose of this study is to explore the efficacy and safety of Inotuzumab Ozogamicin in the treatment of minimal residual disease recurrence after HSCT of ALL patients.

Detailed Description
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As part of postremission consolidative therapy, the decision to proceed with hematopoietic stem cell transplantation is a recommendable regimen in ALL therapy. However, The recurrence rate is high after transplantation. Minimal Residual Disease (MRD) is an important factor affecting the effect of HSCT. The hematologic recurrence rate of MRD-positive patients with adult ALL is high. MRD- is associated with better prognosis. Therefore, maintaining MRD- after transplantation is necessary for long-term survival. INO-VATE confirmed that Inotuzumab Ozogamicin can be used to achieve high remission (CR/CRi) and MRD-negative rates, serving as an effective bridge to HSCT, and it is associated with increased OS and PFS in patients with R/R BCP ALL. The purpose of this study is to explore the efficacy and safety of Inotuzumab Ozogamicin in the treatment of minimal residual disease recurrence after HSCT of ALL patients.

Official Title
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A Multicenter Prospective Clinical Study of Inotuzumab Ozogamicin (INO) in the Treatment of Minimal Residual Disease Recurrent After Hematopoietic Stem Cell Transplantation of Acute Lymphoblastic Leukemia (ALL)

Conditions
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ALL, MRD-positive, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Inotuzumab Ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 15 and ≤ 65 years. Patients diagnosed with CD22+ B-ALL according to 2023 NCCN Acute Lymphoblasts Leukaemias diagnosis standard. CD22+ B-ALL patients with MRD recurrence after HSCT. Ph+ ALL patients were eligible if treatment with 1 or more second-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) had failed, ECOG performance status score less than 3. Expected survival time #3 months. Patients without serious heart, lung, liver, or kidney disease. Ability to understand and voluntarily provide informed consent. Exclusion Criteria: Patients who are allergic to the study drug or drugs with similar chemical structures. Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception. Active infection. Active bleeding. Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment. Patients with mental disorders or other conditions whereby informed consent cannot be obtained and where the requirements of the study treatment and procedures cannot be met. Liver function abnormalities (total bilirubin > 1.5 times the upper limit of the normal range, ALT/AST > 2.5 times the upper limit of the normal range or patients with liver involvement whose ALT/AST > 1.5 times the upper limit of the normal range), or renal anomalies (serum creatinine > 1.5 times the upper limit of the normal value). Patients with a history of clinically significant QTc interval prolongation (male > 450 ms; female > 470 ms), ventricular heart tachycardia and atrial fibrillation, II-degree heart block, myocardial infarction attack within one year before enrollment, and congestive heart failure, and patients with coronary heart disease who have clinical symptoms and requiring drug treatment. Surgery on the main organs within the past six weeks. Drug abuse or long-term alcohol abuse that would affect the evaluation results. Patients who have received organ transplants (excepting bone marrow transplantation). Patients not suitable for the study according to the investigator's assessment.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inotuzumab Ozogamicin in the Treatment of MRD+ After HSCT of ALL<br>intravenous infusion: Cycle 1: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2, if the MRD turn negative, cycle 2: D1 0.5mg/m2, D8 0.5mg/m2, D15 0.5mg/m2， if not，cycle 2: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2 | Drug: Inotuzumab Ozogamicin<br>* intravenous infusion: Cycle 1: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2, if the MRD turn negative, cycle 2: D1 0.5mg/m2, D8 0.5mg/m2, D15 0.5mg/m2， if not，cycle 2: D1 0.8mg/m2, D8 0.5mg/m2, D15 0.5mg/m2<br>* Other names: INO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of MRD- | For Ph-negative ALL: undetectable MRD by flow cytometry At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) . For Ph-positive ALL: undetectable MRD by flow cytometry and absence of quantifiable BCR::ABL1 transcript by PCR At the end of Cycle 1 and Cycle 2(each cycle is 21 days). | At the end of Cycle 1 and Cycle 2(each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | It is measured from the date of entry into this trial to the date of progression or death | 1 year | 
| 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. | 1 year | 
| Adverse events in hematological system | Record of adverse events in hematological system during and after designed venetoclax combined azacitidine regimen induction | 1 year | 
| Adverse events in other organs or systems | Record of adverse events in other organs or systems during and after designed venetoclax combined azacitidine regimen induction. | 1 year |