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

Primary Purpose

B Acute Lymphoblastic Leukemia

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Blinatumomab

About this trial

This is an interventional treatment trial for B Acute Lymphoblastic Leukemia focused on measuring Blinatumomab, Ph-B-ALL, Induction therapy

Eligibility Criteria

15 Years - 59 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The First Affiliated Hospital of Soochow University, Jiangsu Institute of HematologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

reduced-intensity chemotherapy followed by berintuzumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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)

Treatment-related SAE

Incidence of treatment-related severe adverse events, including severe bleeding, infection, drug-related adverse events, and organ dysfunction.

Time of hematopoietic recovery

The duration of the patient in the granulocytic deficiency and thrombocytopenia phases.

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.

Overall survival (OS)

From the time of enrollment in the study to the time of death from any cause.

Full Information

NCT ID

NCT05557110

First Posted

September 16, 2022

Last Updated

May 28, 2023

Sponsor

Chen Suning

1. Study Identification

Unique Protocol Identification Number

NCT05557110

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 8, 2022 (Actual)

Primary Completion Date

August 31, 2023 (Anticipated)

Study Completion Date

October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Chen Suning

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B Acute Lymphoblastic Leukemia

Keywords

Blinatumomab, Ph-B-ALL, Induction therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

reduced-intensity chemotherapy followed by berintuzumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Blinatumomab

Intervention Description

Reduced-intensity chemotherapy followed by Blinatumomab

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

Overall response rate (ORR), including complete response (CR)/ complete response rate with partial hematologic recovery (CRh)/ complete response rate with incomplete hematologic recovery (CRi).

Time Frame

Induction therapy phase: The time of bone marrow evaluation is day 22 or 37±2.

Secondary Outcome Measure Information:

Title

The negative rate of minimal residual lesion (MRD)

Description

The negative rate of minimal residual lesion (MRD) during induction therapy (The threshold is 1×10^-4)

Time Frame

Induction therapy phase: The time of bone marrow evaluation is day 22 or 37±2.

Title

Treatment-related SAE

Description

Incidence of treatment-related severe adverse events, including severe bleeding, infection, drug-related adverse events, and organ dysfunction.

Time Frame

From the beginning of induction therapy to the beginning of consolidation therapy.

Title

Time of hematopoietic recovery

Description

The duration of the patient in the granulocytic deficiency and thrombocytopenia phases.

Time Frame

From the beginning of induction therapy to the beginning of consolidation therapy.

Title

Event-free survival (EFS)

Description

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.

Time Frame

1 year after study completion

Title

Overall survival (OS)

Description

From the time of enrollment in the study to the time of death from any cause.

Time Frame

1 year after study completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

59 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Suning Chen, PHD

Phone

+86-13814881746

chensuning@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jing Lu, Master

Phone

+86-13771836270

lujing@suda.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Suning Chen, PHD

Organizational Affiliation

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Official's Role

Principal Investigator

Facility Information:

Facility Name

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

City

Suzhou

State/Province

Jiangsu

ZIP/Postal Code

215000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Suning Chen, Professor

Phone

13814881746

chensuning@sina.com

First Name & Middle Initial & Last Name & Degree

Suning Chen, Professor

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25385737

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.

Results Reference

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PubMed Identifier

29358182

Citation

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.

Results Reference

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Citation

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).

Results Reference

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

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