Pomalidomide Plus Orelabrutinib and Zuberitamab in Untreated Mantle Cell Lymphoma

A Prospective, Multicenter Clinical Study of Pomalidomide Combined With Orelabrutinib and Zuberitamab in Treatment-Naive Mantle Cell Lymphoma

This multicenter trial evaluates the efficacy and safety of pomalidomide combined with orelabrutinib and zuberitamab (POZ) in patients with mantle cell lymphoma (MCL). After six cycles of POZ, patients who achieved minimal residual disease (MRD) negativity received maintenance therapy with orelabrutinib plus zuberitamab for up to 18 cycles. Those with MRD positivity were excluded and received alternative treatments. The primary endpoint is the MRD rate after six cycles of POZ. Secondary endpoints include progression-free survival (PFS), overall survival (OS), MRD rate, objective response rate (ORR), and safety.

Study Overview

• Status: Recruiting
• Conditions: Mantle Cell Lymphoma (MCL); POZ
• Intervention / Treatment: Drug: Pomalidomide; Drug: Orelabrutinib; Drug: Zuberitamab; Drug: Zuberitamab

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongmei Jing; Phone Number: 86 010-82266781; Email: hongmei_jing@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Peking University Third Hospital
      • Contact: Hongmei Jing; Phone Number: 010-82266778; Email: hongmei_jing@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed mantle cell lymphoma
• Age 18-80 years, both genders are eligible..
• Untreated MCL.
• At least one measurable lesion. Measurable disease is defined as a tumor mass measurable in one or two dimensions ≥1.5 cm, as well as measurable spleen lesions.
• Any one of the following factors is present:: MIPI intermediate-high risk, ki67≥30%, blastoid/pleomorphic, TP53 abnormality (mutation/deletion) or p53 protein expression >50%, large mass (maximum diameter ≥7.5cm), complex karyotype (≥3 chromosomal abnormalities (excluding t(11; 14)))
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

• Hematologic function is adequate, defined as:

  1. Absolute neutrophil count (ANC) ≥1×109/L, growth factor support must not be used within 7 days prior to testing;
  2. Platelet count ≥75×10⁹/L, or ≥50×10⁹/L (if bone marrow involvement), no use of growth factor support or transfusion allowed within 7 days prior to testing.

• Adequate hepatic function per local laboratory reference range as follow:

  1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× the upper limit of normal (ULN);
  2. Bilirubin ≤ 2 × ULN (except for those diagnosed with Gilbert's syndrome, which allows up to 5 × ULN)

• Adequate renal function as demonstrated by:

  1. Creatinine clearance ≥60 mL/min (estimated using the Cockcroft-Gault formula or the glomerular filtration rate [eGFR] estimated using the Modification of Diet in Renal Disease [MDRD] formula)
  2. Serum creatinine ≤1.5×ULN
• International Normalized Ratio (INR) ≤ 1.5 × ULN and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN
• Life expectancy of more than 3 months.
• Ability to provide written informed consent and understand and comply with study requirements.
• Able to comply with the study visit schedule and other protocol requirements

Exclusion Criteria:

• Current central nervous system involvement or suspected patients and those with a history of this condition
• Previously received systemic treatment for MCL, including BTKi.
• Uncontrolled active systemic fungal, bacterial, or viral infections (defined as persistent signs/symptoms related to the infection despite the use of appropriate antibiotics, antiviral therapy, and/or other treatments with no improvement).

• Known human immunodeficiency virus (HIV) infection, or the following serological status indicating active hepatitis B or C virus infection:

  1. Subjects with positive hepatitis B virus core antibody (HBcAb) and negative surface antigen (HBsAg) must have a negative polymerase chain reaction (PCR) result prior to the first dose. Subjects with positive HBsAg or HBV-DNA:
  2. Subjects with positive hepatitis C antibodies must have an HCV-RNA negative result before the first dose. Subjects with positive hepatitis C PCR results will not be eligible for this study.

• Clinically severe cardiovascular diseases, including:

  1. Myocardial infarction occurring within the 6 months prior to screening;
  2. Unstable angina occurring within 3 months prior to screening;
  3. Clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes ventricular tachycardia);
  4. QTcF (corrected by Fridericia's formula) > 480 msec;
  5. History of second-degree type II atrioventricular (AV) conduction block or third-degree atrioventricular conduction block;
  6. III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
• History of severe hemorrhagic disorders, such as hemophilia A, hemophilia B, von Willebrand disease, or a history of spontaneous bleeding requiring blood transfusion or other medical interventions.
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 12 months
• History of significant cerebrovascular disease/events within 6 months prior to the first administration of the investigational drug, including stroke or intracranial hemorrhage.
• Unable to swallow capsules or having significant gastrointestinal functional disorders, such as malabsorption syndrome, gastric or small intestine resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction.
• Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required. If the patient has taken strong or moderate CYP3A inhibitors or inducers within 7 days prior to the first dose of the investigational drug (or has taken these drugs for less than 5 half-lives), they cannot be enrolled. Patients using moderate CYP3A inhibitors can be considered for the study after at least a 7-day washout period.
• Anticoagulation treatment with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) is required within 7 days after the first dose of the investigational drug or receiving anticoagulation therapy.
• Pregnant or breastfeeding women
• Hypersensitivity to any investigational drug
• Any mental or cognitive impairment that may limit their understanding, execution, and compliance with the informed consent form and the study.
• Subjects with drug abuse and alcoholism

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: Pomalidomide + Orelabrutinib + Zuberitamab and Orelabrutinib + Zuberitamab Maintenance; 1. In induction phase, patients will receive pomalidomide 4mg/day PO once daily day1-12/cycle; orelabrutinib 150 mg/day PO once daily; and zuberitamab 375 mg/m² IV on day 1/cycle, every 28 day per cycle for 6 cycles. 2. In maintenance phase, Patients with MRD negative (≤10-5) after induction therapy will recieve orelabrutinib 150 mg/day PO once daily for 18cycles and zuberitamab 375 mg/m² IV on day 1 of cycle 7, 10, 13, 16, 19 and 22, every 28 day per cycle.

Drug: Pomalidomide; 4mg/day PO once daily, day1-21/cycle; Other Names: Induction phase; Drug: Orelabrutinib; 150mg/day PO once daily; Other Names: Induction phase; Drug: Zuberitamab; 375 mg/m² IV on day 1/cycle; Other Names: Induction phase; Drug: Zuberitamab; 375 mg/m² IV on day 1 of cycle 7, 10, 13, 16, 19 and 22,; Other Names: Maintenance phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum residual disease (MRD) rate	After 6 cycles of the pomalidomide combined with orelabrutinib and zuberitamab (POZ) regimen, the proportion of patients with undetectable minimal residual disease (MRD) (≤10-5) as evaluated by the high-throughput sequencing (NGS) platform.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD rate	The proportion of patients with undetectable minimal residual disease (MRD) (≤10-5) as evaluated by the high-throughput sequencing (NGS) platform.	3 months
MRD rate	The proportion of patients with undetectable minimal residual disease (MRD) (≤10-5) as evaluated by the high-throughput sequencing (NGS) platform.	12 months
MRD rate	The proportion of patients with undetectable minimal residual disease (MRD) (≤10-5) as evaluated by the high-throughput sequencing (NGS) platform.	18 months
MRD rate	The proportion of patients with undetectable minimal residual disease (MRD) (≤10-5) as evaluated by the high-throughput sequencing (NGS) platform.	24 months
Overall Response Rate	Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria.	up to 3 years
Progression-free survival	Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	up to 3 years
Overall survival	Overall survival was defined as the time from the date of randomization to the date of death from any cause.	up to 3 years

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: August 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; pomalidomide; orelabrutinib
• Other Study ID Numbers: POZ

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