Pomalidomide, Anti-PD-1 Antibody Combined With Selinexor (PPS) in Relapsed/Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma

April 10, 2026 updated by: LIANG WANG, Beijing Tongren Hospital

Pomalidomide, Anti-PD-1 Antibody Combined With Selinexor (PPS) in Relapsed/Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma: A Prospective, Multicenter, Single-Arm, Phase II Clinical Study

Primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL) is a highly aggressive malignancy accounting for over 80% of primary CNS lymphomas, with an annual incidence of 0.4-0.6 per 100,000 people globally and a rising trend in immunocompetent patients. First-line high-dose methotrexate-based chemotherapy causes severe toxicities and nearly 50% of patients relapse within 1-2 years, developing relapsed/refractory (R/R) disease.

Treatment options for R/R PCNSL are scarce, with low response rates, median survival of only 3-6 months, and 5-year survival below 5%. The blood-brain barrier and tumor heterogeneity further worsen outcomes. This prospective, multicenter, single-arm phase II study evaluates the efficacy and safety of pomalidomide, PD-1 inhibitor, and selinexor (PPS) in R/R PCNSL, aiming to provide a new effective treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL) is a highly aggressive and uncommon extranodal non-Hodgkin lymphoma that exclusively or predominantly involves the central nervous system. As the predominant subtype of primary central nervous system lymphomas, it accounts for more than 80% of all cases, representing a major clinical challenge in neuro-oncology. Epidemiological studies indicate a global annual incidence of 0.4 to 0.6 per 100,000 individuals, with a gradual increase observed in immunocompetent populations in recent decades. This rising incidence, coupled with its malignant biological behavior, has placed substantial pressure on clinical diagnosis and management.

Currently, high-dose methotrexate (HD-MTX)-based combination chemotherapy remains the standard first-line treatment for PCNSL. Some patients may receive consolidation with local radiotherapy or autologous hematopoietic stem cell transplantation to improve disease control. Nevertheless, this therapeutic strategy has significant limitations. High-dose chemotherapy frequently induces severe adverse events, including myelosuppression, liver and renal toxicity, which are poorly tolerated by elderly patients or those with multiple comorbidities. Despite standardized first-line therapy, approximately 50% of patients experience disease relapse or progression within 1 to 2 years, eventually developing relapsed/refractory (R/R) PCNSL.

For patients with R/R PCNSL, therapeutic options are extremely limited. Existing second-line chemotherapy regimens yield unsatisfactory and inconsistent efficacy, with objective response rates generally below 50%. The median overall survival is only 3 to 6 months, and the 5-year survival rate is less than 5%. In addition to poor survival outcomes, patients often suffer from headache, neurological deficits, cognitive impairment, and other neuropsychiatric symptoms, severely impairing quality of life. Furthermore, the physiological barrier of the blood-brain barrier prevents most conventional chemotherapeutic agents from reaching effective intratumoral concentrations. Meanwhile, the high genetic and phenotypic heterogeneity of tumor cells further compromises treatment efficacy and contributes to drug resistance.

Collectively, the clinical demand for safe and effective treatments in R/R PCNSL remains drastically unmet. Therefore, we designed this prospective, multicenter, single-arm phase II clinical trial to systematically investigate the efficacy and safety of the triplet regimen consisting of pomalidomide, PD-1 monoclonal antibody, and selinexor (PPS) in patients with R/R PCNSL-DLBCL. This study aims to establish a novel and practical therapeutic approach, improve survival and quality of life, and fill the current therapeutic gap for this refractory patient population.

Study Type

Interventional

Enrollment (Estimated)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
        • Recruiting
        • Beijing Tongren Hospital, Capital Medical University
        • Principal Investigator:
          • Liang Wang, M.D.
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed primary central nervous system diffuse large B-cell lymphoma (PCNSL-DLBCL).
  • Disease progression or relapse after prior treatment with high-dose methotrexate and/or BTK inhibitors.
  • Age between 18 and 75 years.
  • ECOG performance status score 0-4.
  • Expected overall survival > 3 months.
  • No known hypersensitivity to any study drug.
  • White blood cell count ≥ 3×10⁹/L; absolute neutrophil count ≥ 1.0×10⁹/L; platelet count ≥ 50×10⁹/L.
  • Serum creatinine ≤ 1.5 mg/dL; creatinine clearance ≥ 50 mL/min.
  • ALT and AST ≤ 3× upper limit of normal (ULN); total bilirubin ≤ 2× ULN.
  • Signed written informed consent.

Exclusion Criteria:

  • Presence of another malignant tumor requiring active pharmacological or surgical intervention at present;
  • Female patients who are pregnant or breastfeeding;
  • Patients (male or female) of reproductive potential who are unwilling to use or fail to use effective contraceptive measures;
  • Known hypersensitivity to any study drug or any excipient ingredients of these products;
  • Active infection (determined by the investigator);
  • History of immunodeficiency, including positive HIV status, other acquired or congenital immunodeficiency disorders, or history of organ transplantation;
  • Documented history of neurological or psychiatric disorders, including epilepsy or dementia;
  • Documented history of autoimmune diseases (except Hashimoto's thyroiditis or thyroid dysfunction);
  • Any severe comorbidity that, in the investigator's judgment, would compromise patient safety or interfere with the completion of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PPS group

All enrolled patients may initiate induction therapy after completing baseline imaging and relevant laboratory examinations:

Pomalidomide: 4 mg on days 1-14, every 3 weeks (q3w), for a total of 6 cycles; Selinexor: 60 mg on days 1, 8, and 15, q3w, for a total of 6 cycles; PD-1 monoclonal antibody: tislelizumab 200 mg on day 1, q3w, for a total of 6 cycles.

During induction therapy, patients who achieve complete response (CR) may discontinue from the study to receive consolidation therapy with autologous hematopoietic stem cell transplantation (AHSCT) or dose-optimized whole-brain radiotherapy (WBRT), at the investigator's discretion or the patient's choice.

For patients not discontinuing for consolidation therapy, maintenance therapy may be administered after 6 cycles of induction therapy: pomalidomide 4 mg every other day (qod) plus selinexor 40-60 mg once weekly (qw), until disease progression or unacceptable toxicity.
Drug: Pomalidomide
4 mg on days 1-14, every 3 weeks (q3w), for a total of 6 cycles
Drug: PD-1 / PD-L1 monoclonal antibody
tislelizumab 200 mg on day 1, q3w, for a total of 6 cycles
Drug: XPO1 inhibitor
Selinexor: 60 mg on days 1, 8, and 15, q3w, for a total of 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
best overall response rate (ORR) as of 6 cycles of PPS
Time Frame: From the day of initiation of PPS treatment to 3 weeks after 6 cycles of PPS treatment (the length of each cycle is 3 weeks)
Overall response rate means sum of complete response rate and partial response rate
From the day of initiation of PPS treatment to 3 weeks after 6 cycles of PPS treatment (the length of each cycle is 3 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: From the day of initiation of PPS as of 24 months
PFS was defined from the date of initiation of PPS to the date fo confirmed disease progression or death of any reason
From the day of initiation of PPS as of 24 months
overall survival (OS)
Time Frame: From the day of initiation of PPS as of 24 months
OS was defined from the date of initiation of PPS to the date fo death
From the day of initiation of PPS as of 24 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: From the day of initiation of PPS as of 24 months
measured using CTCAE version 5.0
From the day of initiation of PPS as of 24 months
Best Complete Response rate (CR) as of 6 cycles of PPS
Time Frame: From the day of initiation of PPS treatment to 3 weeks after 6 cycles of PPS treatment (the length of each cycle is 3 weeks)
CR was defined as complete response evaluated using MRI scan
From the day of initiation of PPS treatment to 3 weeks after 6 cycles of PPS treatment (the length of each cycle is 3 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tongren Hospital

Investigators

  • Principal Investigator: Liang Wang, M.D., Beijing Tongren Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

April 6, 2026

First Submitted That Met QC Criteria

April 6, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRhos-PCNSL-01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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