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

• Sponsor: Chen Suning (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05557110
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 11.7
• Patients Per Site Per Month: 3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
B Acute Lymphoblastic Leukemia	Drug: Blinatumomab	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 8, 2022
• Anticipated Primary Completion Date: Mar 1, 2023
• Anticipated Study Completion Date: Aug 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)

2. 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.

3. 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.

4. 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.

5. Overall survival (OS) [1 year after study completion]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 59 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology	Suzhou	Jiangsu	China	215000

Sponsors and Collaborators

• Chen Suning

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Chen Suning, Physician, The First Affiliated Hospital of Soochow University
• ClinicalTrials.gov Identifier: NCT05557110
• Other Study ID Numbers: SZ-ALL02
• First Posted: Sep 27, 2022
• Last Update Posted: Nov 4, 2022
• Last Verified: Nov 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Chen Suning, Physician, The First Affiliated Hospital of Soochow University: Blinatumomab; Ph-B-ALL; Induction therapy
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Blinatumomab

Study Results

No Results Posted as of Nov 4, 2022