Prospective, Single-arm, Multicenter Clinical Study on Haploidentical Hematopoietic Stem Cell Transplantation in Patients With MRD Positive CD19+ALL Treated With Conditioning Regimens Containing Blinatumomab

Study Overview
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Brief Summary
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A study on the effectiveness and safety of haploidentical hematopoietic stem cell transplantation in patients with MRD positive CD19+ ALL treated with conditioning regimens containing Blinatumomab

Detailed Description
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This is a prospective multicenter clinical study. This study is applicable to CD19+ ALL patients undergoing allogeneic hematopoietic stem cell transplantation. The purpose is to evaluate the effectiveness and safety of haploidentical hematopoietic stem cell transplantation in patients with MRD positive CD19+ ALL treated with conditioning regimens containing Blinatumomab.31 patients will be included in the study. Clinical endpoints include progress-free survival, Overall survival, cumulative incidence of relapse, non-relapse mortality, minimal residual disease, and graft versus host disease.

Official Title
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Prospective, Single-arm, Multicenter Clinical Study on Haploidentical Hematopoietic Stem Cell Transplantation in Patients With MRD Positive CD19+ALL Treated With Conditioning Regimens Containing Blinatumomab

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Blinatumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as acute B-ALL with CD19+ according to the 2022 WHO classification criteria. After induction and intensified chemotherapy, complete hematological remission was achieved, but MRD was positive by flow cytometry; Age range from 18 to 70 years old, regardless of gender; The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-2 points; Female patients of childbearing age who had a negative pregnancy test before the trial and agreed to take effective contraceptive measures during the trial until their last visit; Organ function is normal, and the following laboratory indicators are met within one week of enrollment: creatinine clearance rate ≥ 60 mL/min (according to the Cockcroft Fault formula); AST and ALT ≤ 3 × Upper limit of normal value range (ULN), total bilirubin ≤ 2 × ULN; Echocardiography (ECHO) shows left ventricular ejection fraction (LVEF) ≥ 50%; Life expectancy greater than 8 weeks; Voluntarily sign an informed consent form to understand and comply with the requirements of the study. Exclusion Criteria: Failure to achieve complete hematological remission, including residual extramedullary infiltration; Previously received hematopoietic stem cell transplantation; Received systemic chemotherapy within 2 weeks; Previously received treatment with Blinatumomab; Have a history of central nervous system leukemia or present with central nervous system leukemia; Active autoimmune diseases, such as SLE, rheumatoid arthritis, etc; Currently suffering from clinically significant active cardiovascular diseases, such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease determined according to the New York Heart Association (NYHA) functional classification (see Appendix 1), or having a history of myocardial infarction within 6 months prior to screening; Chronic obstructive pulmonary disease with whole lung dysfunction; Other serious diseases that may restrict patients from participating in this test (such as advanced infection, uncontrollable diabetes); Concomitant arteriovenous thrombosis or hypercoagulable state; Known human immunodeficiency virus (HIV) infection, or chronic infection of hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive) beyond drug control; Pregnant or lactating women; Severe allergies to other monoclonal antibodies in the past; Those who are unable to understand, comply with the research protocol or sign an informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Blinatumomab Group<br>Haploidentical hematopoietic stem cell transplantation was performed using a Conditioning regimen containing Blinatumomab. 28ug of Blinatumomab was administered intravenously once a day for a total of 7 days, followed by a routine conditioning regimen and haploid hematopoietic stem cell transplantation. | Drug: Blinatumomab<br>* Haploidentical hematopoietic stem cell transplantation was performed using a Conditioning regimen containing Blinatumomab. 28ug of Blinatumomab was administered intravenously once a day for a total of 7 days, followed by a routine conditioning regimen and haploid hematopoietic stem cell transplantation.<br>* Other names: HSCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-Free Survival | Progression-free survival (PFS) is defined as the time from transplantation to disease progression or death from any cause. | At Year 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival (OS) is defined as the time from transplantation to death | At Year 1 | 
| Cumulative Incidence of Relapse | The time from the date of transplantation to disease recurrence: Disease recurrence, defined as one of the following: Leukemia blasts reappeared in peripheral blood, or blasts ≥ 5%, naive monocytes ≥ 5% in bone marrow, or extramedullary lesions. | At Year 1 | 
| Non-relapse Mortality | NRM was defined as death after transplant that was not preceded by recurrent or progressive malignancy. | At Year 1 | 
| Minimal Residual Disease | Minimal residual disease is a small number of cancer cells left in the body after treatment. | At Year 1 | 
| acute graft versus host disease | assessment of acute GVHD | At Day 100 | 
| chornic graft versus host disease | assessment of chronic GVHD | At Year 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Minimal Residual Disease, Allogeneic hematopoietic stem cell transplantation, Blinatumomab