Methotrexate or Thiotepa Combined With R-CHOP and Orelabrutinib in CNSL Patients

Launched by RUIJIN HOSPITAL · Mar 28, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at the effectiveness and safety of two different treatments, Methotrexate (MTX) and Thiotepa, when combined with a medication called Orelabrutinib and standard chemotherapy for patients with a type of cancer known as diffuse large B-cell lymphoma (DLBCL) that has affected the brain or spinal cord (central nervous system lymphoma). The study is not yet recruiting participants, but it aims to find out how well these treatments work for patients aged 14 to 80 who meet certain health criteria.

To be eligible for this trial, participants need to have a confirmed diagnosis of DLBCL with evidence of central nervous system involvement. They also should be expected to live for at least three more months and have a good overall health status, which includes proper functioning of the bone marrow, liver, and kidneys. Participants will need to agree to follow the study's treatment and visit schedules. It's important to note that individuals with certain health conditions, such as active liver disease or HIV, will not be eligible for this study. If you or a loved one is considering this trial, it could be a chance to access new treatment options and contribute to important research in cancer care.

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Eligibility criteria

• Inclusion Criteria:
• • Fully understand the study and voluntarily sign the informed consent form.
• • Age: 14-80 years.
• • Expected survival of more than 3 months, as determined by the investigator.
• • Pathologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL) of B-cell origin through pathology or flow cytometry.
• * Central nervous system (CNS) involvement, confirmed by at least one of the following:
• • 1. Symptoms related to CNS involvement.
• • 2. Abnormal findings on imaging.
• • 3. Pathological evidence (positive cerebrospinal fluid cytology, positive brain lesion biopsy or positive cerebrospinal fluid ctDNA).
• • Any non-hematologic toxicity related to prior treatments must have resolved to Grade 1 or normal levels (per NCI CTCAE Version 5.0), except for alopecia.
• * Bone marrow and organ function must meet the following criteria (without blood transfusion, G-CSF administration, or pharmacological correction within 14 days prior to screening):
• Bone marrow function:
• • 1)Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L. 2)Platelet count ≥ 50 × 10⁹/L. 3)Hemoglobin ≥ 60 g/L.
• * Liver function:
• • 1. Total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if liver metastasis is present).
• • 2. AST and ALT ≤ 2.5 × ULN (≤ 5.0 × ULN if liver metastasis is present).
• * Coagulation function:
• • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• • • Renal function: Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance rate ≥ 30 mL/min (calculated using the Cockcroft-Gault formula): Male: Cr (mL/min) = (140 - age) × weight (kg) / \[72 × serum creatinine (mg/dL)\]. Female: Cr (mL/min) = (140 - age) × weight (kg) / \[85 × serum creatinine (mg/dL)\].
• • Women of childbearing potential (WOCBP) and men with reproductive potential must agree to use effective contraception during the study and for 3 months after discontinuing treatment.
• • Good compliance, with willingness to adhere to visit schedules, dosing regimens, laboratory tests, and other study procedures.-
• Exclusion Criteria:
• • Contraindications to any of the drugs included in the treatment regimen.
• • History of active liver disease, including viral or other hepatitis or liver cirrhosis (Hepatitis B is defined as HBV-DNA exceeding the upper limit of normal; active Hepatitis C is defined as seropositive for HCV antibodies, but patients with HCV-RNA negative results can be included).
• • Human immunodeficiency virus (HIV) infection.
• • Congestive heart failure classified as greater than NYHA Class II by the New York Heart Association; history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within the past six months.
• • Congenital long QT syndrome or QTc \> 480 ms (Note: QTc must be calculated using Friederica's formula: QTcF = QT / (RR)\^0.33).
• • Pregnant or breastfeeding women, or those planning to become pregnant during the study.
• • History of confirmed neurological or psychiatric disorders, or a history of substance abuse or drug addiction.