RDC-Blinatumomab Versus hyperCVAD for Ph-negative B-ALL. (BEAT-ALL-2024)

Comparing the Efficacy and Safety of Reduced-dose Chemotherapy Followed by Blinatumomab Versus hyperCVAD as Induction Therapy for Newly Diagnosed Ph-negative B-ALL: a Multicenter, Radomized, Phase 2 Study

In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.

Study Overview

• Status: Recruiting
• Conditions: ALL, Adult; Philadelphia-Negative ALL
• Intervention / Treatment: Drug: Blinatumomab Injection [Blincyto]; Drug: Doxorubicin

Detailed Description

Blinatumomab, a CD3/CD19 bisespecific T-cell conjugative antibody, has shown high efficacy in phase I/II studies of relapsed/refractory B-lymphoblastic leukemia (B-ALL), particularly in the context of low tumor burden.Meanwhile, Blinatumomab also plays an important role in rapid and efficient clearance of MRD in patients. Therefore, its use in combination with less intensive chemotherapy for initial induction therapy in newly diagnosed patients may result in favorable response rates, greater depth of remission, and lower treatment-related toxic effects.

In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.

The regimen of consolidation therapy is recommended as multidrug combination chemotherapy (including high-dose Methotrexate or Cytarabine combined with Asparaginase) or alternating with Blinatumomab (28 ug/d×28d). If Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is not performed, consolidation therapy needs at least 4 courses before 2 years maintenance therapy.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing Lu; Phone Number: 1377183627; Email: lujing@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Jing Lu; Phone Number: 1377183627; Email: lujing@suda.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 15-65
• Ph-(BCR-ABL1 negative)B-ALL was diagnosed according to WHO diagnostic criteria
• Newly diagnosed patients without prior induction therapy (except hydroxyurea and glucocorticoids ≦5 days
• ECOG score 0-3
• Liver function: total bilirubin ≦ 3 times the upper limit of normal; Alanine ·aminotransferase ≦ 3 times upper limit of normal motion; Aspartate aminotransferase ≦ 3 times upper limit of normal motion; (except considering leukemia infiltration)
• Renal function: endogenous creatinine clearance ≧30ml/min
• Patients must be able to understand and willing to participate in the study and must sign the informed consent form.

Exclusion Criteria:

• Ph+ (BCR-ABL1 positive) ALL
• T cells ALL
• Mature B-cell leukemia/lymphoma, B-cell lymphoma, with extramedullary disease
• Acute mixed-cell leukemia
• Central nervous system leukemia
• HIV infection
• HBV-DNA or HCV-RNA positive
• Patients with grade 2 or higher heart failure and other patients deemed inappropriate for inclusion by the investigator
• Pregnant or breastfeeding patients
• The study patient was refused enrollment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reduced-dose Chemotherapy Followed by Blinatumomab; Reduced-dose Chemotherapy(including 1 dose of Idarubicin 8 mg/m2, 1 dose of Vincristine 1.4 mg/m2[max 2mg], and 7 days of Dexamethasone 9 mg/m2/d) followed by 2 weeks of Blinatumomab (9 ug/d d8-14, 28 ug/d d15-21) immediately. If not achieved CR/CRi, Blinatumomab 28 ug for another 14 days should be continued.	Drug: Blinatumomab Injection [Blincyto]; Reduced-intensity chemotherapy followed by Blinatumomab
Active Comparator: hyperCVAD; CTX 300mg/m2 q12h D1-3 VCR 1.4mg/m2 (max 2mg) D4,D11 DNR 50mg/m2, D4 DEX 40mg/d D1-4, D11-14	Drug: Doxorubicin; HyperCVAD regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission rate	CR/CRi	Induction therapy phase: The time of bone marrow evaluation is day 28±7.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	From the time of enrollment in the study to the time of death from any cause.	1 year after study completion
The negative rate of minimal residual lesion (MRD)	The negative rate of minimal residual lesion (MRD) during induction therapy (The threshold is 1×10^-4)	Induction therapy phase: The time of bone marrow evaluation is day 28 ±7.
Treatment-related AE	Incidence of treatment-related adverse events, including severe bleeding, infection, drug-related adverse events, and organ dysfunction.	Induction therapy phase
Quality of survival of patients in the induction therapy phase	QLQ-C30 Survival Quality Scale	Induction therapy phase
Progression-free survival（PFS）	The time from random assignment in a clinical trial to disease progression or death from any cause.	1 year after study completion

Collaborators and Investigators

• Sponsor: Chen Suning
• Investigators: Principal Investigator: Jing Lu, MD, Soochow U

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Blinatumomab
• Other Study ID Numbers: BEAT-ALL-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol, Basic Statistical Analysis
• IPD Sharing Time Frame: 1 year after the publication of the summary paper
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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