CNS Prophylaxis in Diffuse Large B-cell Lymphoma
Study Evaluating Relapses in Central Nervous System in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy With or Without CNS Prophylaxis. Multicentric, Prospective, Randomized Phase III Study
  • Phase

    Phase 3
  • Study Type

  • Status

    Unknown status
  • Intervention/Treatment

    naltrexone ...
  • Study Participants

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).
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.
Study Started
Jul 31
Primary Completion
Dec 31
Study Completion
Dec 31
Last Update
Jun 06

Drug Methotrexate

i.v. or intrathecal CNS prophylaxis

  • Other names: Methotrexate,manufactured by EBEWE, Methotrexate, manufactured by HOSPIRA

Arm A - Methotrexate i.v. Experimental

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. Active Comparator

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).

Arm C - no Methotrexate No Intervention

Patients with 0-1 risk factor for CNS relapse will not receive CNS prophylaxis.


Inclusion Criteria:

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

Exclusion Criteria:

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
No Results Posted