CNS Prophylaxis in Diffuse Large B-cell Lymphoma
- Registration Number
- NCT02777736
- Lead Sponsor
- Czech Lymphoma Study Group
- Brief Summary
Comparison of cumulative incidence of CNS relapses in patients with diffuse large B-cell lymphoma with intermediate or high risk of CNS relapse treated with CNS prophylaxis: either with 2 doses of intravenous methotrexate 3g/m2 i.v.(arm A) or 6 doses of intrathecal methotrexate 12mg (arm B) and in patients with low risk of CNS relapse without CNS prophylaxis (arm C).
- Detailed Description
Patients with diffuse large B-cell lymphoma are evaluated for risk factors of CNS relapse during initial staging (age \> 60years, lactate dehydrogenase (LDH) \> reference range, clinical stage III/IV, performance status according to Eastern Cooperative Oncology Group (ECOG) \>1, kidney and/or adrenal gland involvement, involvement \> 1 extranodal organ) including evaluation of cerebrospinal fluid.
All patients with systemic DLBCL without CNS involvement are treated with systemic chemotherapy: either 6 cycles of R CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednison) +2xR (rituximab) or 6 cycles of DA EPOCH R (dose adjusted etoposide, prednison, vincristin, cyclophosphamide, doxorubicin) +2xR (rituximab). Patients with ≥ 2 risk factors for CNS relapse or with occult meningeal involvement will be randomized in 1:1 ratio either into arm A with 2 cycles of prophylactic methotrexate 3g/m2 i.v., or into arm B with prophylactic 6x intrathecal methotrexate 12mg (1x intrathecal methotrexate in each cycle of systemic chemotherapy). Patients with 0-1 risk factor will be allocated into arm C without CNS prophylaxis. Patients will be observed for CNS relapse during the follow-up of 1year after the end of the first-line treatment.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 500
- histologically confirmed DLBCL
- age 18-72 years
- signed informed consent with the study
- first-line treatment 6 cycles of R CHOP +2x R or 6 cycles of DA EPOCH R+ 2xR
- DLBCL and concomitant initial CNS involvement
- PMBL (primary mediastinal B-cell lymphoma)
- treatment with another chemotherapy than R CHOP or DA EPOCH R
- HIV positive, or active hepatitis B or C
- other concomitant serious disease (based on the decision of the physician-investigator)
- non-compliance of a patient
- any contraindication for application of anthracycline based chemotherapy or high dose methotrexate
- pregnancy or breast-feeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A - Methotrexate i.v. Methotrexate Patients with risk factors for CNS relapse ≥ 2 or with occult meningeal involvement will receive 2 cycles of methotrexate 3g/m2 i.v. after the 3rd and 6th cycle of systemic chemotherapy (R CHOP or DA EPOCH R). Arm B - Methotrexate i.t. Methotrexate Patients with risk factors for CNS relapse ≥ 2 or with occult meningeal involvement will receive intrathecal methotrexate 12mg in each cycle of systemic chemotherapy (6x).
- Primary Outcome Measures
Name Time Method Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis 1 year
- Secondary Outcome Measures
Name Time Method Overall response rate 1 year Overall survival 2 years Progression-free survival 2 years Complete remission rate 1 year
Trial Locations
- Locations (6)
University Hospital Hradec Králové
🇨🇿Hradec Králové, Czech Republic
University Hospital Brno-Bohunice
🇨🇿Brno, Czech Republic
University Hospital Ostrava
🇨🇿Ostrava, Czech Republic
University Hospital Kralovske Vinohrady
🇨🇿Prague, Czech Republic
University Hospital Pilsen
🇨🇿Pilsen, Czech Republic
General University Hospital Prague
🇨🇿Prague, Czech Republic