Reduced-dose Chemotherapy Followed by Blinatumomab in Induction Therapy of Newly Diagnosed Non-elderly Ph-B-ALL

Study Overview
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Brief Summary
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Blinatumomab, a CD3/CD19 bisespecific T-cell conjugative antibody, has shown high efficacy in phase I/II studies of relapsed/refractory B-lymphoblastic leukemia (B-ALL), particularly in the context of low tumor burden.Meanwhile, Blinatumomab also plays an important role in rapid and efficient clearance of MRD in patients. Therefore, its use in combination with less intensive chemotherapy for initial induction therapy in newly diagnosed patients may result in favorable response rates, greater depth of remission, and lower treatment-related toxic effects. In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and treated with reduced-intensity chemotherapy followed by Blinatumomab as the basis of induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated in newly diagnosed non-elderly PH-B-ALL patients during induction therapy.

Official Title
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A Multicenter, Single-arm, Open-end Study of Reduced-dose Chemotherapy Followed by Blinatumomab in Induction Therapy of Newly Diagnosed Non-elderly Philadelphia Chromosome Negative Acute B Lymphoblastic Leukemia

Conditions
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B 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: Age 15-59 Ph-(BCR-ABL1 negative)B-ALL was diagnosed according to WHO diagnostic criteria Newly diagnosed patients without prior induction therapy (except hydroxyurea and glucocorticoids ≦5 days) ECOG score 0-3 Liver function: total bilirubin ≦ 3 times the upper limit of normal; Alanine aminotransferase ≦ 3 times upper limit of normal motion; Aspartate aminotransferase ≦ 3 times upper limit of normal motion; (except considering leukemia infiltration) Renal function: endogenous creatinine clearance ≧30ml/min Patients must be able to understand and willing to participate in the study and must sign the informed consent form. Exclusion Criteria: Ph+ (BCR-ABL1 positive) ALL and known ABL class Ph-Like ALL T cells ALL Mature B-cell leukemia/lymphoma, B-cell lymphoma, isolated extramedullary disease Acute mixed-cell leukemia Central nervous system leukemia HIV infection HBV-DNA or HCV-RNA positive Patients with grade 2 or higher heart failure and other patients deemed inappropriate for inclusion by the investigator Pregnant or breastfeeding patients The study patient was refused enrollment

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: reduced-intensity chemotherapy followed by berintuzumab<br>Induction therapy was performed with reduced intensity chemotherapy (including 1 dose of Idarubicin 8 mg/m2, 1 dose of Vindesine 3 mg/m2, and 7 days of Dexamethasone 9 mg/m2/d) followed by 2 weeks of Blinatumomab (9 ug/d d8-14, 28 ug/d d15-21) immediately. Bone marrow evaluation was performed on day 22±2, and consolidation therapy was performed after achieving bone marrow remission (CR/CRh/CRi). If CR/CRh/CRi was not achieved in the first course of induction therapy, Blinatumomab (28ug/d×14d) should be continued and bone marrow evaluation should be evaluated again. The regimen of consolidation therapy is recommended as multidrug combination chemotherapy (including high-dose Methotrexate or Cytarabine combined with Asparaginase) or alternating with Blinatumomab (28 ug/d×28d). If Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is not performed, consolidation therapy needs at least 4 courses before 2 years maintenance therapy. | Drug: Blinatumomab<br>* Reduced-intensity chemotherapy followed by Blinatumomab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Overall response rate (ORR), including complete response (CR)/ complete response rate with partial hematologic recovery (CRh)/ complete response rate with incomplete hematologic recovery (CRi). | Induction therapy phase: The time of bone marrow evaluation is day 22 or 37±2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The negative rate of minimal residual lesion (MRD) | The negative rate of minimal residual lesion (MRD) during induction therapy (The threshold is 1×10^-4) | Induction therapy phase: The time of bone marrow evaluation is day 22 or 37±2. | 
| Treatment-related SAE | Incidence of treatment-related severe adverse events, including severe bleeding, infection, drug-related adverse events, and organ dysfunction. | From the beginning of induction therapy to the beginning of consolidation therapy. | 
| Time of hematopoietic recovery | The duration of the patient in the granulocytic deficiency and thrombocytopenia phases. | From the beginning of induction therapy to the beginning of consolidation therapy. | 
| Event-free survival (EFS) | The time from enrollment to the occurrence of any event, including death, progression of disease, change in treatment regimen, and occurrence of fatal or intolerable side effects. | 1 year after study completion | 
| Overall survival (OS) | From the time of enrollment in the study to the time of death from any cause. | 1 year after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blinatumomab, Ph-B-ALL, Induction therapy