Pomalidomide Plus Orelabrutinib and Zuberitamab in Untreated Mantle Cell Lymphoma

NCT07257510 | Recruiting

• 1 other identifier: POZ
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mantle Cell Lymphoma (MCL); POZ

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• MRD rate

  3 months

• MRD rate

  12 months

• MRD rate

  18 months

• MRD rate

  24 months

• Overall Response Rate

  up to 3 years

Study Arms (1)

Pomalidomide + Orelabrutinib + Zuberitamab and Orelabrutinib + Zuberitamab Maintenance

EXPERIMENTAL

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; Drug: Orelabrutinib; Drug: Zuberitamab

Interventions

Pomalidomide DRUG

4mg/day PO once daily, day1-21/cycle

Also known as: Induction phase

Pomalidomide + Orelabrutinib + Zuberitamab and Orelabrutinib + Zuberitamab Maintenance

Orelabrutinib DRUG

150mg/day PO once daily

Also known as: Induction phase

Pomalidomide + Orelabrutinib + Zuberitamab and Orelabrutinib + Zuberitamab Maintenance

Zuberitamab DRUG

375 mg/m² IV on day 1/cycle

Also known as: Induction phase

Pomalidomide + Orelabrutinib + Zuberitamab and Orelabrutinib + Zuberitamab Maintenance

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) ≥1×109/L, growth factor support must not be used within 7 days prior to testing;
• 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:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× the upper limit of normal (ULN);
• Bilirubin ≤ 2 × ULN (except for those diagnosed with Gilbert's syndrome, which allows up to 5 × ULN)
• Adequate renal function as demonstrated by:
• 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)
• Serum creatinine ≤1.5×ULN

You may not qualify if:

• 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:
• 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:
• 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:
• Myocardial infarction occurring within the 6 months prior to screening;
• Unstable angina occurring within 3 months prior to screening;
• Clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes ventricular tachycardia);
• QTcF (corrected by Fridericia's formula) \> 480 msec;
• History of second-degree type II atrioventricular (AV) conduction block or third-degree atrioventricular conduction block;
• 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

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

pomalidomide; orelabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Hongmei Jing

CONTACT

86 010-82266781; hongmei_jing@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)