Blinatumomab as a Bridge to Allo-HSCT in HR BCP-ALL

Study Overview
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Brief Summary
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To explore the efficacy and safty of Blinatumomab as a bridge to Allogeneic Hematopoietic Stem Cell Transplantation in High Risk Precursor B-cell Acute Lymphoblastic Leukemia

Detailed Description
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High Risk Precursor B-cell Acute Lymphoblastic Leukemia is a kind of leukemia with poor prognosis. Here, we want to explore the efficacy and safty of Blinatumomab as a bridge to Allogeneic Hematopoietic Stem Cell Transplantation in High Risk Precursor B-cell Acute Lymphoblastic Leukemia.

Official Title
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A Multicenter ,Prospective, Randomized Clinical Trial of Blinatumomab As a Bridge to Allogeneic Hematopoietic Stem Cell Transplantation in High Risk Precursor B-cell Acute Lymphoblastic Leukemia

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Blinatumomab
* Other: Conventional therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients meet the diagnostic criteria for high risk precursor B-ALL (according to the 2016 WHO classification) and are under hematologic remission. ECOG score is 0-2. Expecting life span is more than 6 months. Patients are free from severe organ dysfunction. Exclusion Criteria: Patients are combined with severe organ dysfunction: Organ failure: Cardiac failure: ejection fraction(EF) <30%, NYHA standard, cardiac function not Full Grade II or above; Liver and kidney insufficiency: serum total bile Erythroid ≥2mg/dl, AST or ALT≥ upper limit of normal 2.5-fold, serum creatinine (SCr) >2.5mg/ dL or blood Creatinine clearance rate < 30ml/min. Patients are combined with infection or other complications that can not tolerate chemotherapy. Patients are suffering from central nervous system/solitary extramedullary leukemia. Patients are considered as tumer progression. Patients has undergone allogeneic hematopoietic stem cell transplantation or underwent autologous stem cell transplantation within 6 weeks or other immunotherapy within 4 weeks. Pregnant and lactating women will not be included.

Ages Eligible for Study
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Minimum Age: 14 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinatumomab arm<br>On the 1st to 3rd day, Blinatumomab should be continuous intravenous use for 24 hours with 9ug/ day for those whose weight are equal to or greater than 45kg, and 5ug/ m2 / day for those whose weight are less than 45kg (maximum dosage is 9ug/ day) per 24 hours. On the 4th to 14th day, for the patients who are equal to or greater than 45kg, they will receive Blinatumomab at the dose of 28ug/ day with continuous intravenous administration, and those below 45kg are given a 24h continuous infusion of 15ug/ m2 / day (maximum dose is 28ug/ day). Bucy-based myeloablative conditioning regimen will be performed on the 15th day. | Drug: Blinatumomab<br>* Blinatumomab will be bridged to conventional BUCY conditioning regimen.<br>|
| Other: Conventional therapy<br>Bucy-based myeloablative conditioning regimen will be given to those patients are enrolled into control group. | Other: Conventional therapy<br>* Control group will be given conventional BUCY conditioning regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time from randomization to death from any cause. | From the 1st day to the 720th days after enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with negative minimal residual disease (MRD) | Negative MRD is defined as below 10-4 by flow cytometry. | From the 1st day to the 720th days after enrollment. | 
| Progression-Free Survival (PFS) | It is defined as the total survival of a patient after the hematopoietic stem cell transplantation, until the tumor recurrence or death from any cause. | From the 1st day to the 720th days after enrollment. | 
| Cumulative incidence of relapse (CIR) | From hematopoietic stem cell transplantation to recurrence, relapse-free death was considered a competing risk event. | From the 1st day to the 720th days after enrollment. |