Clinical trial NCT06504186: The Use of Blinatumomab in Patients With NGS-MRD Relapsed B-ALL After Autologous/Allogeneic Transplantation
Official title: A Prospective, Single-arm Clinical Study of the Use of Blinatumomab in Patients With NGS-MRD Relapsed B-ALL After Autologous/Allogeneic Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: B-ALL
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-07-16
Enrollment: 20
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: disease-free survival (DFS)
timeFrame: Follow-up until 3 years after transplantation
measure: recurrence rate
timeFrame: Follow-up until 3 years after transplantation
Secondary outcomes:
measure: NGS-MRD response rate
timeFrame: 3 and 6 months after transplantation and at 15 days after treatment
measure: overall survival (OS)
timeFrame: Follow-up until 3 years after transplantation
measure: incidence of acute and chronic GVHD
timeFrame: 100 days after transplantation
Other outcomes:
Locations:
Study officials:
References: