Blinatumomab Maintenance After Allo-HSCT

Efficacy and Safety of Blinatumomab Maintenanceafter Allogeneic Hematopoietic Stem Cell Transplantation for High-risk Acute B-lymphoblastic Leukemia: a Multicenter, Open-label, Randomized Controlled Study

To evaluate the safety and efficacy of Blinatumomab maintenance after allogeneic hematopoietic stem cell transplantation for high-risk acute B-lymphoblastic leukemia.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab

Detailed Description

Blinatumomab is a novel immunological antibody based on BiTE. CD19 is a surface antigen expressed throughout the development of B lymphocytes, making it an ideal target for immunotherapy. Blinatumomab was approved by the FDA for the treatment of adults with relapsed/refractory cancers. Open-label, single-arm, multicenter phase II clinical study (BLAST study) , enrolling 116 adult patients with precursor B-ALL in complete hematologic remission after at least 3 doses of intense chemotherapy but persistently positive for Measurable Residual Disease (MRD) (MRD ≥10-3 ), which is the first ALL international multicenter clinical trial. In August 2022, China's National Medicines and Pharmaceutical Administration (NMPA) Approved Blinatumomab for the treatment of relapsed/refractory precursor B-cell ALL in adults.

Blinatumomab is mostly used for preemptive therapy after post-transplant MRD conversion, and fewer prospective studies have been conducted in the area of maintenance therapy. A prospective single-arm clinical study (NCT02807883) with Blinatumomab as maintenance therapy (up to 4 cycles) after allogeneic transplantation, concluded by MD Anderson in August 2021, had the primary endpoints of safety (acute graft-versus-host disease [aGVHD] and non-relapse mortality [NRM]) and the secondary endpoints of efficacy (PFS, OS, etc.), a total of 23 patients were enrolled in patients who received at least 1 cycle of Blinatumomab, the interval between transplantation and the first cycle of Blinatumomab use was 78 days (44-105), 57% of the patients completed 4 cycles of treatment, the median follow-up was 14.3 months, the 1-year NRM was 0%, the incidence of grade 3-4 aGVHD was 5%, the 1-year OS was 85%, and the 1-year PFS was 71%. There was a trend toward benefit in PFS and OS curves between the two groups. Although this study is an exploratory study, data from applied studies in the post-transplantation maintenance phase suggest that this immunotherapy may be termed as a new, better and safer option.

Therefore, the investigators conducted a multicenter, randomized, controlled study based on retrospective research to further explore and validate the safety and efficacy of Blinatumomab as a maintenance therapy after high-risk B-ALL allogeneic transplantation.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 16-65 years
2. Diagnosis with acute B-lymphoblastic leukemia (B-ALL) expressed CD19
3. High-risk group B-ALL
4. Have suitable hematopoietic stem cell donors
5. No dysfunction of vital organs

Exclusion Criteria:

1. CR/MRD negative before blinatumomab maintenance
2. Active hepatitis B
3. HIV-infected
4. Active infections; acute and chronic GVHD requiring systemic immunosuppressive therapy;
5. severe impairment of vital organ function
6. Those judged by the investigator to be unsuitable for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinatumomab group; Blinatumomab group (Blinatumomab): 9 μg/d intravenously over 24 hours until the end of d14 days of dosing. Repeat every 3 months for a total of 4 courses. (Basis for Dose Selection: The recommended dose of blinatumomab for MRD-negative patients is 9ug/d)	Drug: Blinatumomab; Maintenance therapy with Blinatumomab initiation: 90 days to 120 days post-transplantation
No Intervention: Control group; Maintenance therapy in the control group was based on the routine maintenance therapy in each center (including but not limited to decitabine, sorafenib, prophylactic DLI, except for all types of CD19 mono- and dual-antibodies and CD22-ADC drugs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year Event-free survival	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
2-year relapse rate	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): June 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: TROPHY-ALL01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No