Diffuse Large B-Cell Lymphoma (DLBCL), Intrathecal Chemotherapy
Conditions
Brief summary
This is a prospective, single-arm clinical study to evaluate the efficacy and safety of intrathecal thiotepa for the prevention of central nervous system (CNS) involvement in patients with high-aggressive B-cell lymphoma. A total of 32 subjects will be enrolled, and the study is planned to last for 2 years. Outcomes including CNS recurrence rate, time to CNS involvement, progression-free survival (PFS), overall survival (OS), and safety parameters will be assessed during the study.
Interventions
DRUG(RCHOP or an investigator's choice) plus IT thiotepa and dexamethasone
Patients received standard immunochemotherapy (RCHOP or an investigator's choice) plus IT thiotepa (10 mg) and dexamethasone (5 mg) via LP on day 1 of each cycle for at least four cycles. Following LP, patients remained supine for 4-6 hours. CSF analyses were repeated with each IT administration. Concomitant HD-MTX was permitted for patients enrolled in parallel protocols and was accounted for in sensitivity analyses.
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation in the clinical study: full understanding of the study, provision of written informed consent, willingness and ability to comply with all study procedures. 2. Age ≥ 18 years, male or female. 3. Histopathologically confirmed high-grade B-cell lymphoma, including: diffuse large B-cell lymphoma (DLBCL), NOS; T-cell/histiocyte-rich large B-cell lymphoma; EBV-positive DLBCL, NOS; primary mediastinal large B-cell lymphoma; ALK-positive large B-cell lymphoma; high-grade B-cell lymphoma, NOS; high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements. 4. No prior anti-tumor therapy including chemotherapy, radiotherapy, immunotherapy, or other anti-lymphoma treatments. 5. Intermediate or high risk of central nervous system (CNS) involvement (meeting any one of the following): 1. Primary breast lymphoma or primary testicular lymphoma; 2. Involvement of any of the following sites: testis, breast, kidney, adrenal gland, paranasal sinus, epidural space, uterus; 3. CNS-IPI score ≥ 4; 4. Double-protein expression of MYC (≥40% positive) and BCL2 (≥50% positive); 5. Gene rearrangements of MYC, BCL2 and/or BCL6. 6. ECOG performance status ≤ 2. 7. Life expectancy ≥ 3 months. 8. No evidence of CNS involvement (no brain parenchymal lesions on MRI and no malignant cells in CSF). 9. Adequate organ and bone marrow function without severe hematologic, cardiac, pulmonary, hepatic, renal dysfunction or immunodeficiency: 1. Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet ≥ 75 × 10⁹/L, hemoglobin ≥ 9.0 g/dL. If bone marrow is involved: platelet ≥ 50 × 10⁹/L, ANC ≥ 1.0 × 10⁹/L, hemoglobin ≥ 8.0 g/dL. 2. Hepatic function: serum bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN (≤ 5 × ULN if liver involvement). 3. Renal function: serum creatinine ≤ 1.5 × ULN. 4. Coagulation: INR ≤ 1.5 × ULN; PT and APTT ≤ 1.5 × ULN (unless on therapeutic anticoagulation with values within expected range). 10. Negative serum pregnancy test for females of childbearing potential. Effective contraception required from informed consent until 6 months after the last chemotherapy. 11. Negative ophthalmologic evaluation, including dilated fundoscopy, slit-lamp examination, and color fundus photography.
Exclusion criteria
1. History of other malignancy within the past 5 years. 2. Burkitt lymphoma, primary central nervous system lymphoma, or B-cell lymphoma transformed from indolent lymphoma. 3. Existing brain parenchymal or meningeal lymphoma involvement. 4. Patients who have received any form of CNS prophylaxis. 5. Patients who have received whole-brain radiotherapy or craniospinal irradiation. 6. Patients with obstructive hydrocephalus requiring neurosurgical intervention. 7. Presence of any of the following known infections or conditions: 1. Active meningeal infection 2. Known human immunodeficiency virus (HIV) infection 3. Active tuberculosis 4. Active autoimmune disease 5. Interstitial lung disease or infectious pneumonia 8. Patients whose underlying conditions, in the investigator's judgment, may increase the risk associated with study drug treatment or confound the evaluation of adverse reactions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year cumulative incidence of SCNS relapse | At 2 years after baseline (total study duration: 2 years) | 2-year cumulative incidence of SCNS relapse (isolated or combined with systemic progression), adjudicated by an independent radiologic-neurologic panel. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | At 2 years after baseline (total study duration: 2 years) | 2-year progression-free survival (PFS) |
| OS | At 2 years after baseline (total study duration: 2 years) | 2-year overall survival (OS) |
| Safety | Day 1 of each cycle, and at the end of each treatment cycle,and 30 days after the last dose of study treatment. | Safety assessments were performed at baseline, on Day 1 of each cycle, and at the end of each treatment cycle. Additional safety evaluations were conducted 30 days after the last dose of study treatment |
Countries
China
Outcome results
None listed