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

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

Study Purpose

This study is designed as an open-label, prospective, single-arm, single-center trial aimed at evaluating the efficacy and safety of MTX or Thiotepa combined with Orelabrutinib and standard chemotherapy regimens in the treatment of DLBCL patients with central nervous system involvement.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	14 Years - 80 Years
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06901999
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Ruijin Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	CNS Lymphoma

Arms & Interventions

Arms

Experimental: MTX or Thiotepa(for MTX-Intolerant Patients) Combined with R-CHOP and Orelabrutinib therapy group

For DLBCL patients with central nervous system involvement, administer methotrexate (MTX) or thiotepa (for patients intolerant to MTX) combined with R-CHOP and orelabrutinib for six cycles, with each cycle lasting 21 days. Following the completion of induction therapy, proceed with consolidation therapy. If the patient undergoes autologous stem cell transplantation, maintain orelabrutinib for one year; if not, maintain orelabrutinib for two years unless disease progression or intolerable toxicity occurs.

Interventions

Drug: - Orelabrutinib

150 mg qd po. D1-21, 6 cycles, 21 days per cycle For patients continue transplant, maitaining for 1 year follow-up; otherwise maintaining during 2 years of follow-up，unless disease progression or intolerable toxicity occurs.

Drug: - RCHOP+MTX or Thiotepa

rituximab: 375 mg/m2, D0; cyclophosphamide: 750 mg/m2, D1; doxorubicin: 50 mg/m2, D1; vincristine: 1.4 mg/m2, D1; prednisone: 100 mg, D1-5; MTX: 3.5 g/m2, D0; Thiotepa: 40 mg/m2, D3; Induction therapy, 6 cycles, 21 days a cycle