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

Phase 2

Completed

• Conditions: B Acute Lymphoblastic Leukemia
• Interventions: Drug: Blinatumomab

• Registration Number: NCT05557110
• Lead Sponsor: Chen Suning

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-08
• Study First Submitted: 2022-09-16
• Study First Submitted QC: 2022-09-25
• Study First Posted: 2022-09-27
• Primary Completion: 2024-01-05
• Study Completion: 2024-03-31
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-11
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Age 15-65
2. Ph-(BCR-ABL1 negative)B-ALL was diagnosed according to WHO diagnostic criteria
3. Newly diagnosed patients without prior induction therapy (except hydroxyurea and glucocorticoids ≦5 days)
4. ECOG score 0-3
5. 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)
6. Renal function: endogenous creatinine clearance ≧30ml/min
7. Patients must be able to understand and willing to participate in the study and must sign the informed consent form.

Exclusion Criteria

1. Ph+ (BCR-ABL1 positive) ALL and known ABL class Ph-Like ALL
2. T cells ALL
3. Mature B-cell leukemia/lymphoma, B-cell lymphoma, isolated extramedullary disease
4. Acute mixed-cell leukemia
5. Central nervous system leukemia
6. HIV infection
7. HBV-DNA or HCV-RNA positive
8. Patients with grade 2 or higher heart failure and other patients deemed inappropriate for inclusion by the investigator
9. Pregnant or breastfeeding patients
10. The study patient was refused enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
reduced-intensity chemotherapy followed by berintuzumab	Blinatumomab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology; 🇨🇳 Suzhou, Jiangsu, China