IT-TT as an Effective and Well-Tolerated Strategy for CNS Prop in High-Risk DLBCL: a Prospective Ph II Study

NCT07493486 | Completed Phase 2

• 1 other identifier: IRB-2022-9
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B-Cell Lymphoma (DLBCL); Intrathecal Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 2-year cumulative incidence of SCNS relapse

  2-year cumulative incidence of SCNS relapse (isolated or combined with systemic progression), adjudicated by an independent radiologic-neurologic panel.

  At 2 years after baseline (total study duration: 2 years)

Secondary Outcomes (3)

• PFS

  At 2 years after baseline (total study duration: 2 years)

• OS

  At 2 years after baseline (total study duration: 2 years)

• Safety

  Day 1 of each cycle, and at the end of each treatment cycle,and 30 days after the last dose of study treatment.

Study Arms (1)

(RCHOP or an investigator's choice) plus IT thiotepa and dexamethasone

EXPERIMENTAL

Drug: (RCHOP or an investigator's choice) plus IT thiotepa and dexamethasone

Interventions

(RCHOP or an investigator's choice) plus IT thiotepa and dexamethasone DRUG

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.

(RCHOP or an investigator's choice) plus IT thiotepa and dexamethasone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years, male or female.
• 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.
• No prior anti-tumor therapy including chemotherapy, radiotherapy, immunotherapy, or other anti-lymphoma treatments.
• Intermediate or high risk of central nervous system (CNS) involvement (meeting any one of the following):
• Primary breast lymphoma or primary testicular lymphoma;
• Involvement of any of the following sites: testis, breast, kidney, adrenal gland, paranasal sinus, epidural space, uterus;
• CNS-IPI score ≥ 4;
• Double-protein expression of MYC (≥40% positive) and BCL2 (≥50% positive);
• Gene rearrangements of MYC, BCL2 and/or BCL6.
• ECOG performance status ≤ 2.
• Life expectancy ≥ 3 months.
• No evidence of CNS involvement (no brain parenchymal lesions on MRI and no malignant cells in CSF).
• Adequate organ and bone marrow function without severe hematologic, cardiac, pulmonary, hepatic, renal dysfunction or immunodeficiency:

You may not qualify if:

• History of other malignancy within the past 5 years.
• Burkitt lymphoma, primary central nervous system lymphoma, or B-cell lymphoma transformed from indolent lymphoma.
• Existing brain parenchymal or meningeal lymphoma involvement.
• Patients who have received any form of CNS prophylaxis.
• Patients who have received whole-brain radiotherapy or craniospinal irradiation.
• Patients with obstructive hydrocephalus requiring neurosurgical intervention.
• Presence of any of the following known infections or conditions:
• Active meningeal infection
• Known human immunodeficiency virus (HIV) infection
• Active tuberculosis
• Active autoimmune disease
• Interstitial lung disease or infectious pneumonia
• 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.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD,Principal Investigator

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 25, 2026
• Study Start: February 1, 2022
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

CN (1)