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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

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

Study contacts

• Study coordinator: Li Wang
• Email: wl-wangdong@126.com
• Phone: +86 15214370575

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.