The Use of Blinatumomab in Patients With NGS-MRD Relapsed B-ALL After Autologous/Allogeneic Transplantation

NCT ID: NCT06504186

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2026-10-31

Brief Summary

To explore the efficacy and safety ofblinatumomab± TKI in B-ALL patients aged ≥ 14 years with NGS-MRD relapse (sensitivity: 10-6) after auto/allo HSCT, and to observe the disease-free survival (DFS), recurrence rate and toxicity after transplantation.

Detailed Description

To explore the efficacy and safety ofblinatumomab± TKI in B-ALL patients aged ≥ 14 years with NGS-MRD relapse (sensitivity: 10-6) after auto/allo HSCT, and to observe the disease-free survival (DFS), recurrence rate and toxicity after transplantation.

Primary endpoint: disease-free survival (DFS), recurrence rate Secondary endpoints: NGS-MRD response rate, overall survival (OS), incidence of acute and chronic GVHD, and summary and evaluation of physical examination, vital signs, adverse events, concomitant treatments, and laboratory abnormalities.

• Ph-negative B-ALL: bephedolumab (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Ph-positive B-ALL: treatment with bephytoin + TKIs, bephytoin (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Premedication with dexamethasone:

3)For adults, premedication with dexamethasone 20 mg was administered 1 hour prior to the first dose of each cycle ofblinatumomab, prior to dose escalation (eg, Cycle 1 Day 8), and when the infusion was restarted 4 hours or more after treatment interruption.

4)Pediatric patients were pre-treated with dexamethasone 5 mg/m2 up to a maximum of 20 mg prior to the first dose ofblinatumomabduring Cycle 1, prior to dose escalation (eg, Cycle 1 Day 8), and when the infusion was resumed 4 hours or more after interruption of therapy during Cycle 1.

Conditions

B-ALL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

NGS-MRD relapsed B-ALL after autologous/allogeneic transplantation

• Ph-negative B-ALL: bephedolumab (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Ph-positive B-ALL: treatment with bephytoin + TKIs, bephytoin (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Premedication with dexamethasone:

3)For adults, premedication with dexamethasone 20 mg was administered 1 hour prior to the first dose of each cycle ofblinatumomab, prior to dose escalation (eg, Cycle 1 Day 8), and when the infusion was restarted 4 hours or more after treatment interruption.

Pediatric patients were pre-treated with dexamethasone 5 mg/m2 up to a maximum of 20 mg prior to the first dose ofblinatumomabduring Cycle 1, prior to dose escalation (eg, Cycle 1 Day 8), and when the infusion was resumed 4 hours or more after interruption of therapy during Cycle 1

Group Type: OTHER

Blinatumomab

Intervention Type: DRUG

• Ph-negative B-ALL: bephedolumab (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Ph-positive B-ALL: treatment with bephytoin + TKIs, bephytoin (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.

Interventions

Blinatumomab

• Ph-negative B-ALL: bephedolumab (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.
• Ph-positive B-ALL: treatment with bephytoin + TKIs, bephytoin (≥ 45 kg: 9 mcg/d D1-2, 28 mcg/d D3-14 or 28 mcg/d D1-14; < 45 kg: 5 mg/m2/d D1-2, 15 mg/m2/d D3-14) in 28-day cycles for 3 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1.CD19 + acute B-lymphoblastic leukemia (Ph- or Ph + ALL); 2.Age ≥ 14 years, male or female 3.B-ALL includes any of the following:

1. The cytogenetic prognosis of adult acute B lymphoblastic leukemia in accordance with NCCN 2023 at initial diagnosis was divided into poor prognosis group;

2. Patients with relapsed and refractory ALL and MRD-positive ALL before transplantation,

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1. Refractory ALL is one of the following conditions. A）Failure to achieve CR/CRi at the end of induction therapy (generally referred to as 4-week regimen or Hyper-CVAD regimen).

2. Relapsed ALL is defined as the appearance of blasts in the peripheral blood or bone marrow (> 5%), or the development of extramedullary disease in patients who have achieved CR.

3. A positive MRD before transplantation is one of the following conditions. A）Proportion of abnormal blasts > 0.01% by flow cytometry within 45 days prior to transplantation B）Positive molecular biology related tests before transplantation; 4.NGS-IGH Conspicuous Clonal Sequences Collected (Timepoint: At initial diagnosis or prior to transplant) 5.MRD relapse (≥ 10-6, IGH-VDJ rearrangement by NGS) and < 5% bone marrow blasts at 3 and 6 months post auto/allo HSCT 6.ECOG score of 0 or 1/≤ 2 7.Adequate organ function (ALT/AST < 5 x upper limit of normal (ULN), serum bilirubin < 3.0 x ULN, creatinine clearance > 30ml/min) 8.Negative test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), and hepatitis C virus (anti-HCV) 9.Negative pregnancy test for women of childbearing potential 10.Awareness and willingness to sign written informed consent

Exclusion Criteria

• Subjects who met any of the following criteria were not to be enrolled in the study: 6.CNSL or other extramedullary involvement after transplantation, other malignancies 7.Relevant central nervous system pathology (eg, seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or coordination or dyskinesia) 8.Co-infection active 9.Concomitant active GVHD requiring treatment 10.Product component allergy 11.Treatment with an investigational product 4 weeks prior to treatment

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

erlie jiang, MD

Role: CONTACT

jiangerlie@ihcams.ac.cn

+86-15122538106

Other Identifiers

IIT2024044

Identifier Type: -

Identifier Source: org_study_id