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

B Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05557110
• Other study ID #: SZ-ALL02
• Status: Completed
• Phase: Phase 2
• Start date: September 8, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: April 2024
• Source: The First Affiliated Hospital of Soochow University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: March 31, 2024
• Est. primary completion date: January 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 15-59

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

Related Conditions & MeSH terms

• B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blinatumomab
Reduced-intensity chemotherapy followed by Blinatumomab

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Chen Suning

Country where clinical trial is conducted

China, 

References & Publications (3)

Fleming, S. et al. Sequential Blinatumomab with Reduced Intensity Chemotherapy in the Treatment of Older Adults with Newly Diagnosed Ph Negative B-Precursor Acute Lymphoblastic Leukemia - Interim Analysis of the Australasian Leukemia and Lymphoma Group ALL08 Study. Blood 138, 1234-1234, doi:10.1182/blood-2021-151826 (2021).

Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. Erratum In: Blood. 2019 Jun 13;133(24):2625. — View Citation

Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014 Dec 20;32(36):4134-40. doi: 10.1200/JCO.2014.56.3247. Epub 2014 Nov 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	Overall survival (OS)	From the time of enrollment in the study to the time of death from any cause.	1 year after study completion