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

A Prospective, Single-arm Clinical Study of the Use of Blinatumomab in Patients With NGS-MRD Relapsed B-ALL After Autologous/Allogeneic Transplantation

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.

Study Overview

• Status: Not yet recruiting
• Conditions: B-ALL
• Intervention / Treatment: Drug: Blinatumomab

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: erlie jiang, MD; Phone Number: +86-15122538106; Email: jiangerlie@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 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

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival (DFS)	disease-free survival (DFS)	Follow-up until 3 years after transplantation
recurrence rate	recurrence rate	Follow-up until 3 years after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 and 6 months after transplantation and at 15 days after treatment
overall survival (OS)	overall survival (OS)	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.	100 days after transplantation

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: IIT2024044

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No