Trial | NCT02777736  Report issue

Title

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

    Interventional

  • Status

    Unknown status

  • Intervention/Treatment

    naltrexone ...

  • Study Participants

    500
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
2015
Primary Completion
Dec 31
2018
Anticipated
Study Completion
Dec 31
2019
Anticipated
Last Update
Jun 06
2016
Estimate

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.

Criteria 

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