Zanubrutinib Combined With BEAM for ASCT in Relapsed and Refractory DLBCL

A Single-center, Randomized Controlled Clinical Study of Zanubrutinib Combined With Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preconditioning Regimen for ASCT in Relapsed and Refractory DLBCL

This trial is a prospective, single-center, randomized controlled clinical research. The intention is to evaluate the efficacy and safety of zanubrutinib combined with BEAM as a pretreatment regimen for ASCT in relapsed and refractory DLBCL patients through prospective clinical studies.

Study Overview

• Status: Not yet recruiting
• Conditions: DLBCL
• Intervention / Treatment: Drug: zanubrutinib combined with BEAM; Drug: BEAM

Detailed Description

This trial includes 66 patients with recurrent or refractory DLBCL, who will be randomly divided into a 1:1 combination of zanubrutinib and BEAM regimen pretreatment (experimental group) or a standard BEAM regimen pretreatment (control group), and then undergo ASCT treatment. The entire trial includes a screening period (before the start of autologous stem cell transplantation pretreatment), a treatment period (-8 days to -2 days, a total of 7 days), and a follow-up period (2 years after autologous stem cell transplantation)

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei-Li Zhao, professor; Phone Number: +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Meng-Meng Ji, doctor; Phone Number: +862164370045; Email: jimengmeng025@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. According to world Health Organization (WHO) classification of disease, diffuse large B-cell lymphoma was confirmed by histology, CR or PR after second-line and above treatment;
2. 18≤ age ≤65 years old, male or female;
3. ECOG score 0-2;

4. No serious organic lesions in the main organs, meeting the requirements of the following laboratory examination indicators (conducted within 7 days before treatment) :

   1. White blood cell count ≥3.0×109/L, absolute neutrophil count ≥1.5×109/L, Hemoglobin ≥90g/L, platelet ≥75×109/L;
   2. Total bilirubin ≤1.5× upper normal value (ULN);
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× ULN; Bilirubin ≤1.5× ULN
   4. Creatinine clearance was 44-133 mmol/L;
5. No cardiac dysfunction;
6. Life expectancy over 3 months;
7. The subject or his/her legal representative must provide written informed consent prior to conducting a special study examination or procedure.

Exclusion Criteria:

1. Previously received autologous hematopoietic stem cell transplantation;
2. Suffering from serious complications or severe infection;
3. Previous treatment with selinexor;
4. Central nervous system lymphoma was excluded;
5. A history of other malignant tumors within 5 years, excluding early tumors treated for curative purposes;
6. Patients with uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc.;
7. HBsAg, HCV or HIV positive. Positive HBV and HCV serology is allowed, but DNA/RNA testing must be negative;
8. Left ventricular ejection fraction ≦ 50%;

9. Laboratory test value during screening;

   ① Neutrophils <1.5×109/L; Platelet <75×109/L;

   ② Bilirubin was 1.5 times higher than the normal upper limit, transaminase was 2.5 times higher than the normal upper limit;

   ③ The creatinine level is higher than 1.5 times the upper limit of normal value;

10. Other concurrent and uncontrolled medical conditions considered by the investigator would affect the patient's participation in the study;
11. Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol;
12. Pregnant or lactating women;
13. The researcher judged that the patients were not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zanubrutinib combined with BEAM; zanubrutinib combined with camustine, etoposide, cytarabine, and mafaran (BEAM)	Drug: zanubrutinib combined with BEAM; zanubrutinib：160mg oral bid D-8-D-2 camustine: 300mg/m2 vgtt qd D-8 etoposide: 100mg/m2/d vgtt q12h D-7-D-4 cytarabine: 200mg/m2/d vgtt q12h D-7-D-4 melphalan: 140mg/m2 vgtt qd D3-D-2
Active Comparator: BEAM; camustine, etoposide, cytarabine, and mafaran (BEAM)	Drug: BEAM; camustine: 300mg/m2 vgtt qd D-8 etoposide: 100mg/m2/d vgtt q12h D-7-D-4 cytarabine: 200mg/m2/d vgtt q12h D-7-D-4 melphalan: 140mg/m2 vgtt qd D3-D-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival was defined as the time from the data of ASCT until the date of the first documented day of disease progression or relapse, using Lugano criteria, or death from an cause, whichever occured first.	Baseline up to data cut-off (up to approxiamately 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival was defined as the time from the date of ASCT to the date of death from any cause	Baseline up to data cut-off (up to approxiamately 2 years)
Complete remission rate	Percentage of participants with complete response was determined on 2014 Lugano criteria	3 months after the transplantation
The time of hematopoietic reconstruction	The first day of neutrophils ≥0.5*109/L for 3 consecutive days was the time of successful implantation of granulocytes. Platelet ≥20.0*109/L for 7 consecutive days and the first day after platelet infusion was considered as the successful time of megakaryocytes implantation	2 months after the transplantation
Transplantation-related adverse reactions	Transplantation-related adverse reactions are any untoward medical occurrence in a participant which is related to ASCT.	Baseline up to data cut-off (up to approxiamately 4 years)

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 21, 2024
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: ASCT-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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