ZSDT for the Treatment of R/R Mantle Cell Lymphoma After BTK Inhibitor Failure: a Multi-center Prospective Clinical Trial

ZSDT for the Treatment of Recurrent Refractory Mantle Cell Lymphoma After BTK Inhibitor Failure: a Multi-center Prospective Clinical Trial

For relapsed/refractory mantle cell lymphoma patients that previously treated with BTK inhibitors: The first part involves 6 cycles of combined therapy with zuberitamab, selinexor, dexamethasone, and thalidomide. This targeted combination regimen can enhance efficacy while reducing toxic side effects. The second part utilizes Zuberitamab plus selinexor for maintenance consolidation therapy, thereby reducing relapse and prolonging survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Mantle Cell Lymphoma (MCL)
• Intervention / Treatment: Drug: ZSDT regimen

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhang; Phone Number: 13938247096; Email: liyananread@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • the First Affiliated Hospital of Zhengzhou University
      • Contact: Mingzhi Zhang, Professor; Phone Number: 13938247096; Email: liyananread@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Ages 18-70, ECOG score 0-2(including ages 18 and 70);
2. Overall Survival > 6 months;
3. The diagnosis of mantle cell lymphoma was confirmed by histopathology. 4.At least one measurable lesion;

5.Acceptable hematologic parameters, no contraindications to chemotherapy, absolute neutrophil ≥1.0 × 10 ^ 9 L, platelet ≥75 × 10 ^ 9 L, hemoglobin ≥80 g/L (except for patients with bone marrow infiltration) 6.Liver function: direct bilirubin ≤1.5 × upper limit , Alanine transaminase or aspartate transaminase ≤2.5 × upper limit , Alkaline phosphatase≤3 × ULN in patients without non-bone involvement 7.Renal function: serum creatinine ≤1.5 ×ULN 5; 8.Women of Childbearing Potential (WOBCP) or men and their WOBCP partners should agree to take effective contraceptive measures from the signing of ICF and WOBCP must undergo a serum pregnancy test within seven days before the first medication and the results are negative; 9.Recurrent refractory patients after BTK inhibitor treatment; 10.The subjects voluntarily participate the study.

Exclusion Criteria:

1. Refusing to take blood samples;
2. Previous allergies to any of the medications in the regimen;
3. Pregnant and lactating women;
4. The researchers believe that major diseases can cause interference in the trial.;
5. Combined with other tumors.;
6. There are drug-related contraindications to treatment in the protocol;
7. People with severe mental illness;
8. Participating in other clinical trials;
9. Other serious diseases that may limit the subject's participation in this trial, such as: uncontrolled diabetes mellitus; Severe cardiac insufficiency (NYHA classification II or above); Acute coronary syndrome within the past 6 months; Coronary revascularization such as stenting, coronary artery bypass surgery, and other heart and large vessel related surgeries in the past 6 months; Severe arrhythmias include frequent premature ventricular episodes, ventricular tachycardia, rapid atrial fibrillation/atrial flutter, and severe bradycardia. Uncontrolled hypertension: systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg. Gastric ulcer (gastric ulcer judged by the investigator to be at risk of perforation); Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, autoimmune thrombocytopenia, etc.); Severe respiratory diseases (such as obstructive pulmonary disease and history of bronchospasm), etc.;
10. In the opinion of the investigators, it is not suitable for enrollment;
11. Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer test is not within the normal reference value; Those who are positive for hepatitis C virus (HCV) antibody and positive for hepatitis C virus (HCV) RNA in peripheral blood; Those who are positive for human immunodeficiency virus (HIV) antibodies; Those who test positive for syphilis.

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: ZSDT regemin; This study enrolled 30 patients with relapsed refractory mantle cell lymphoma (MCL). The treatment protocol included: selinexor 60mg once daily on days 1 and 8, zuberitamab 375 mg/m² on day 0, Dexamethasone 20 mg on days 1-3 and 8-9, and thalidomide 200 mg on days 1-21. Each treatment cycle lasted 21 days, with six consecutive cycles. Patients achieving complete remission (CR) or partial response (PR) would receive a year-long maintenance therapy of zuberitamab 375 mg/m² every three months and selinexor 60 mg daily on days 1 and 8. Patients experiencing disease progression (PD) would be excluded from the study.

Drug: ZSDT regimen; The study is based on the R2 protocol and preclinical and clinical studies of selinexor. For relapsed refractory MCL patients who had received BTK inhibitors: selinexor 60mg once daily on days 1 and 8, zuberitamab 375 mg/m² on day 0, Dexamethasone 20 mg on days 1-3 and 8-9, and thalidomide 200 mg on days 1-21. Each treatment cycle lasted 21 days, with six consecutive cycles. Patients achieving complete remission (CR) or partial response (PR) would receive a year-long maintenance therapy of zuberitamab 375 mg/m² every three months and selinexor 60 mg daily on days 1 and 8. Patients experiencing disease progression (PD) would be excluded from the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	comple remission rate	From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

• Sponsor: Zhengzhou University
• Investigators: Principal Investigator: Professor Zhang, The first affliated hospital of ZhengZhou University

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Mantle-Cell
• Other Study ID Numbers: 2025-KY-0057-004

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