Central Nervous System Lymphoma, Diffuse Large B Cell Lymphoma
Conditions
Keywords
central nervous system prophylaxis, methotrexate
Brief summary
Central nervous system (CNS) relapse is a devastating event of diffuse large B cell lymphoma (DLBCL). It occurs in 4%-7% of DLBCL in general and the rate is considerably higher in high-risk patients, resulting in a poor outcome.Effective methods of CNS prophylaxis have not yet been developed. Evidence for intrathecal or intravenous MTX are both controversial. In one previous study of PUMCH, IV MTX at a dose of 1g/m2 could significantly decrease the 2 year CNS relapse rate of high risk DLBCL(1.1% vs 12.1% for historic cohort, P=0.003). In current study, the investigators are aiming to confirm its efficacy through phase III study with intrathecal MTX as the controlled arm.
Detailed description
In this prospective, phase III, multicenter, randomized, controlled study, the investigatirs aim to compare the efficacy of intravenous MTX(IV arm) at a dose of 1g/m2 with intrathecal MTX(IT arm) in terms of preventing CNS relapse. All the patients will recieve RCHOP regimen as front-line treatment of DLBCL. Patients in IV arm will recieve 4 course of IV MTX, which is incorporated into the RCHOP, naming R-MTX-CHOP regimen. Patients in IT arm will be given intrathecal MTX for 4 courses (one time for each course). 2 year CNS relapse rate is the primary endpoint while 2 year PFS, 2 year OS and safety are the secondary endpoint.
Interventions
DRUGMethotrexate
intravenous versus intrathecal methotrexate
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age ≥ 18 years * with high CNS risk, which was defined as involvement of more than one extranodal site, or involvement of particular extranodal sites such as bone marrow, breasts, testes, paranasal sinuses, epidural space, adrenal glands, kidney and female genital system; * first-line treatment planned to be RCHOP * absence of CNS involvement at presentation
Exclusion criteria
* primary CNS lymphoma * already have CNS involvement at diagnosis * primary mediastinal lymphoma, intravascular large B-cell lymphoma, DLBCL leg-type, Burkitt lymphoma, high-grade lymphomas, double expressor lymphoma * with active infection or other malignancy * severe liver or kidney insufficiency * allergy to any medication we plan to use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 year CNS relapse rate | 2 year | CNS relapse was defined as positive CSF conventionalcytology, CSF flow cytometry, or biopsy. For those who had clinical symptoms indicating a CNS involvement and typical lesions on MRI, the investigators also considered a recurrence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | 2 year | from diagnosis to any event including progression, relapse and death |
| overall survival | 2 year | from diagnosis to death |
Countries
China
Contacts
Primary ContactWei Wang, MD.
Backup ContactDaobin Zhou, MD.
Outcome results
None listed