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

N/ANot Yet RecruitingNCT06504186

Institute of Hematology & Blood Diseases Hospital, China20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

B-ALL

Interventions

BlinatumomabDRUG

* 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.

Eligibility

Sex: ALLMin age: 14 Years

Medical Language ↔ Plain English

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,  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

Outcomes

Primary Outcomes

disease-free survival (DFS)

Time frame: Follow-up until 3 years after transplantation

recurrence rate

Time frame: Follow-up until 3 years after transplantation

Secondary Outcomes

NGS-MRD response rate

Bone marrow was collected from patients at 3 and 6 months after transplantation and at 15 days after treatment with blinatumomab, and immunoglobulin rearranged IGH-VDJ sequences were monitored using high-throughput sequencing (NGS) to identify significant clonal sequences to regularly determine changes in MRD levels before and after treatment.

Time frame: 3 and 6 months after transplantation and at 15 days after treatment

overall survival (OS)

Time frame: Follow-up until 3 years after transplantation

incidence of acute and chronic GVHD

The frequency and severity of acute GVHD of the intestine, skin, and liver were observed until 100 days after transplantation, and all episodes of GVHD were graded using the clinical grading criteria for acute GVHD. The changes of skin, liver function, eyes, and oral cavity of patients after 100 days after transplantation were observed to assess the incidence of localized and extensive chronic GVHD.

Time frame: 100 days after transplantation

Central Contacts

erlie jiang, MD

CONTACT

+86-15122538106 jiangerlie@ihcams.ac.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.