Orelabrutinib and selinexor with methotrexate, thiotepa, or temozolomide for relapsed or refractory CNS lymphoma

A Clinical Study on the Efficacy and Safety of Methotrexate (MTX) or Thiotepa (for MTX Intolerance) or Temozolomide (TMZ) Combined With Orelabrutinib and Selinexor in Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma（SELINA）

This trial will try adding oral orelabrutinib and selinexor to methotrexate (or thiotepa if MTX can't be used, or temozolomide) to see if it helps people with relapsed or refractory primary or secondary CNS lymphoma.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: Orelabrutinib, chemotherapy, Methotrexate, rituximab, ibrutinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07191431 on ClinicalTrials.gov

What this trial studies

This is an open‑label, prospective, single‑arm, single‑center trial at Ruijin Hospital testing the combination of orelabrutinib and selinexor with either high‑dose methotrexate, thiotepa (for MTX intolerance), or temozolomide in patients with relapsed or refractory B‑cell primary or secondary CNS lymphoma. Eligible participants are aged 14–80, must have B‑cell CNS lymphoma confirmed by pathology or flow cytometry, and must have received at least one prior systemic therapy for CNS lesions while meeting preset organ‑function and marrow criteria. The primary focus is on treatment efficacy and safety, with planned monitoring of response rates, progression, and chemotherapy‑related toxicities during and after therapy. As a single‑arm, nonrandomized study, results will be descriptive and intended to inform larger trials and treatment decisions.

Who should consider this trial

Good fit: People aged 14–80 with relapsed or refractory B‑cell primary or secondary CNS lymphoma who have had at least one prior systemic therapy for CNS lesions and meet the study's organ function and safety criteria are eligible.

Not a fit: Patients with non‑B‑cell lymphoma, severe organ dysfunction, life expectancy under three months, or those unable to attend the single center for treatment are unlikely to benefit from participation.

Why it matters

Potential benefit: If effective, this combination could increase response rates and offer better disease control for patients with relapsed or refractory CNS lymphoma who have few options.

How similar studies have performed: BTK inhibitors combined with CNS‑directed chemotherapy (for example, ibrutinib with methotrexate‑based regimens) have shown promising signals in PCNSL, but the specific pairing of orelabrutinib plus selinexor with MTX/thiotepa/TMZ is novel and has limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Patients must meet all of the following criteria to be enrolled in this study:
* Fully understand this study and voluntarily sign the informed consent form;
* Age: 14-80 years;
* Life expectancy judged by the investigator to exceed 3 months;
* B-cell origin central nervous system lymphoma (CNSL) confirmed by pathology or flow cytometry (histology or cytology);
* Relapsed or refractory PCNSL or SCNSL: Must have received at least one prior systemic therapy for CNS lesions; number of relapses is not restricted;
* Any non-hematological toxicity related to prior treatment should have recovered to Grade 1 or normal (according to NCI CTCAE version 5.0, except alopecia).
* Bone marrow and organ function meeting the following criteria (no transfusion, no G-CSF use, no medication for correction within 14 days before screening):

Bone marrow function: Absolute neutrophil count ≥1.0x10⁹/L, platelets ≥50x10⁹/L, hemoglobin ≥60g/L;Liver function: Serum total bilirubin ≤1.5xULN (≤3.0xULN if liver metastases present); AST and ALT ≤ 2.5xULN (≤5.0xULN if liver metastases present);Coagulation function: International Normalized Ratio (INR) and activated partial thromboplastin time ≤1.5xULN;Renal function: Serum creatinine ≤1.5xULN or estimated creatinine clearance ≥30 mL/min (Male: Cr (mL/min) = (140 - age) x weight (kg) / (72 x serum creatinine (mg/dL)); Female: Cr (mL/min) = (140 - age) x weight (kg) / (85 x serum creatinine (mg/dL))).

* Female subjects of childbearing potential and male subjects with reproductive ability, who have no pregnancy plan with their partners during the study period and for 3 months after treatment interruption, must use one of the following effective contraceptive methods throughout the study and for 3 months after treatment interruption: abstinence, physical contraception (e.g., ligation, condoms, etc.), hormonal contraceptive drugs started at least 3 months before the first dose in the study. Male subjects are prohibited from sperm donation from the start of treatment until 3 months after treatment cessation. The patient or their legal guardian voluntarily signs the informed consent form.
* Good compliance, willing to adhere to the visit schedule, dosing plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

* Patients who meet any of the following criteria will not be allowed to enter this study:
* Contraindication to any drug in the treatment regimen;
* Subject has a history of active liver disease, including viral or other hepatitis or cirrhosis (Hepatitis B defined as HBV-DNA above the upper limit of normal; active Hepatitis C defined as seropositive for HCV antibody, but those with negative HCV-RNA can be enrolled);
* Human Immunodeficiency Virus (HIV) infection;
* Congestive heart failure (New York Heart Association Class \>2); history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within the past six months;
* Hereditary long QT syndrome or QTc \>480ms (Note: QTc interval must be calculated using Fridericia's formula, QTcF = QT/(RR)\^0.33);
* Pregnant and lactating women, or those planning to become pregnant during the study period;
* Clear history of neurological or psychiatric disorders, or history of psychotropic drug abuse or drug addiction;
* Clinically significant active infection.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Li Wang

Conditions Lymphoma Cns; lymphoma CNS; Selinexor