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

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

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.

Study Overview

• Status: Completed
• Conditions: B Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 55 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: reduced-intensity chemotherapy followed by berintuzumab; 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; Reduced-intensity chemotherapy followed by Blinatumomab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chen Suning
• Investigators: Principal Investigator: Suning Chen, PHD, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Publications and helpful links

General Publications

• Lu J, Qiu H, Wang Y, Zhou X, Dai H, Lu X, Yang X, Gu B, Hong M, Miao M, Lu R, Wang J, Wu Q, Xue M, Wang Y, Deng A, Shen Y, Liu Y, Dou X, Lei Y, Wu D, Zhu Y, Chen S. Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial. J Hematol Oncol. 2024 Sep 2;17(1):79. doi: 10.1186/s13045-024-01597-8.

Helpful Links

• 2024EHA; P409

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2022
• Primary Completion (Actual): January 5, 2024
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 25, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Blinatumomab; Induction therapy; Ph-B-ALL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: SZ-ALL02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes