Blinatumomab Combined With Venetoclax as Maintenance Therapy After Allo-HSCT in High-risk Ph Negative Acute B-cell Lymphoblastic Leukemia

Blinatumomab Combined With Venetoclax as Maintenance Therapy After Allo-HSCT in High-risk Ph Negative Acute B-cell Lymphoblastic Leukemia：a Prospective，Single-arm Study

This study is a single-center, single-arm, prospective clinical trial evaluating the efficacy and safety of blinatumomab combined with venetoclax as maintenance therapy for high-risk Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation .

Study Overview

• Status: Active, not recruiting
• Conditions: B-Cell Acute Lymphoblastic Leukemia, Adult
• Intervention / Treatment: Drug: blinatumomab combined with venetoclax as maintenance therapy

Detailed Description

This study focuses on high-risk Philadelphia chromosome-negative (Ph-) acute B-cell lymphoblastic leukemia (B-ALL) patients. The primary objective is to evaluate the efficacy of blinatumomab combined with venetoclax as maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients, while the secondary objective is to assess its safety. The primary endpoint is the 2-year progression-free survival (PFS) rate post-transplantation. Secondary endpoints include the 2-year cumulative relapse rate, 2-year overall survival (OS), incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative incidence of chronic GVHD, graft-versus-host disease-free and relapse-free survival (GRFS), non-relapse mortality (NRM), and the incidence of treatment-emergent adverse events (TEAEs) (defined as occurring from the start of maintenance therapy to 3 months after completion). Safety assessments include the incidence of adverse events and serious adverse events during treatment.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • First Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Demographics : Patients aged 14-65 years, regardless of gender or race.
• Diagnosis : Confirmed Ph-negative acute B-cell lymphoblastic leukemia (Ph- B-ALL) through bone marrow cytomorphology, cytochemistry, immunophenotyping, chromosomal analysis, and genetic mutation testing, with CD19 surface antigen expression.
• Risk Stratification :

High-risk B-ALL (per NCCN 2024.V2 guidelines) or Standard-risk B-ALL with no pre-transplant remission or Standard-risk B-ALL in first complete remission (CR1) with measurable residual disease (MRD) positivity or Standard-risk B-ALL with ≥CR2 or B-ALL patients receiving reduced-intensity or non-myeloablative conditioning.

• Transplant Eligibility : Scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a suitable donor meeting: HLA-identical sibling donor or Unrelated donor (HLA 9-10/10 high-resolution matched) or Haploidentical related donor.
• HCT-CI Score : ≤2 (Hematopoietic Cell Transplantation-Specific Comorbidity Index).
• ECOG Performance Status : ≤2.
• Organ Function :

Serum creatinine ≤1.5×ULN Cardiac ejection fraction ≥50% Baseline SpO₂ >92% Total bilirubin ≤1.5×ULN; ALT/AST ≤2.0×ULN Pulmonary DLCO (hemoglobin-adjusted) ≥40% and FEV1 ≥50%

• Post-Transplant Recovery :

Full donor chimerism Platelet count >50×10⁹/L Absolute neutrophil count >1.0×10⁹/L Hemoglobin >80g/L - Informed Consent : Patient and legal guardian must provide written informed consent, comply with treatment protocols, follow-up visits, and laboratory assessments.

Exclusion Criteria:

• Prior Malignancy : History of malignancy other than acute lymphoblastic leukemia within 5 years, except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer post-radical resection, or ductal carcinoma in situ post-resection.
• MRD-Negative B-ALL : Standard-risk B-ALL with MRD-negative status pre-transplant (per NCCN 2024.V2).
• Disease Activity : Relapse of primary disease or CR/MRD positivity (≥0.01%) confirmed by bone marrow re-evaluation within 1 week before maintenance therapy.
• T-Cell Deficiency : Absolute CD3+ T-cell count ≤0.5×10⁹/L prior to maintenance therapy.
• Active GVHD : Concurrent acute/chronic GVHD requiring systemic immunosuppressive treatment.
• Unstable Systemic Diseases : Including but not limited to:
• Unstable angina or cerebrovascular accident/transient ischemic attack (within 3 months)
• Myocardial infarction (within 3 months)
• Congestive heart failure (NYHA Class ≥ III)
• Post-pacemaker implantation with severe arrhythmia requiring medication
• Uncontrolled hepatic/renal/metabolic diseases
• Pulmonary hypertension
• Active Infection : Uncontrolled infections requiring intravenous antibiotics. HIV : Positive human immunodeficiency virus status. Hepatitis : Active HBV/HCV requiring antiviral therapy.
• Psychiatric Conditions : Mental disorders or inability to provide informed consent.
• Substance Abuse : Drug addiction or chronic alcoholism affecting trial evaluation.
• Reproductive Status :

Pregnant/breastfeeding females Fertile patients unwilling to use contraception during treatment and 12 months post-treatment

- Other : Conditions deemed inappropriate by investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: blinatumomab combined with venetoclax as maintenance therapy; blinatumomab combined with venetoclax as maintenance therapy for high-risk Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation	Drug: blinatumomab combined with venetoclax as maintenance therapy; blinatumomab combined with venetoclax as maintenance therapy for high-risk Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the 2-year progression-free survival (PFS) rate post-transplantation	evaluate the 2-year progression-free survival (PFS) rate post-transplantation of blinatumomab combined with venetoclax as maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients	the 2-year progression-free survival (PFS) rate post-transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
the 2-year cumulative relapse rate	2 year after allogeneic hematopoietic stem cell transplantation (allo-HSCT)
2-year overall survival (OS)	2 year after allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Study Director: Hongyan Tong, First Affiliated Hospital, Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: September 9, 2025
• First Submitted That Met QC Criteria: September 28, 2025
• First Posted (Estimated): September 30, 2025

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Venetoclax; B-cell Acute Lymphoblastic Leukemia; Blinatumomab; Allogeneic Hematopoietic Stem Cell Transplantation; maintenance therapy; Philadelphia chromosome-negative
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Burkitt Lymphoma; Health Care Facilities Workforce and Services; venetoclax; Maintenance
• Other Study ID Numbers: IIT20250105C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• 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