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

NCT06901999 | Not Yet Recruiting Phase 2

• 1 other identifier: CNSL-WL-001
• Study Type: interventional
• Target: 23
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

CNS Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  The CR rate is defined as the percentage of participants with CR, on the basis of investigator assessments, according to 2014 Lugano criteria.

  the end of Cycle 6 (up to approximately 24 weeks)

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  up to approximately 4 years

• The Overall Response Rate (ORR)

  the end of Cycle 6 (up to approximately 24 weeks)

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Orelabrutinib; Drug: RCHOP+MTX or Thiotepa

Interventions

Orelabrutinib DRUG

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.

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

RCHOP+MTX or Thiotepa DRUG

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

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

Eligibility Criteria

• Age: 14 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Symptoms related to CNS involvement.
• Abnormal findings on imaging.
• 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:
• )Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L. 2)Platelet count ≥ 50 × 10⁹/L. 3)Hemoglobin ≥ 60 g/L.
• Liver function:
• Total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if liver metastasis is present).
• AST and ALT ≤ 2.5 × ULN (≤ 5.0 × ULN if liver metastasis is present).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Interventions

orelabrutinib; Thiotepa

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Weili Zhao, Prof.

CONTACT

+86 2164370045; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: March 30, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share