Clinical trial NCT02777736: CNS Prophylaxis in Diffuse Large B-cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Lymphoma, B cell
Central nervous system relapse
Methotrexate
Intrathecal chemotherapy
Lead sponsor: Czech Lymphoma Study Group
Sponsor class: OTHER
First posted: 2016-05-19
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis
timeFrame: 1 year
Secondary outcomes:
measure: Complete remission rate
timeFrame: 1 year
measure: Overall response rate
timeFrame: 1 year
measure: Overall survival
timeFrame: 2 years
measure: Progression-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: University Hospital Brno-Bohunice
city: Hradec Králové
country: Czech Republic
facility: University Hospital Hradec Králové
city: Ostrava
country: Czech Republic
facility: University Hospital Ostrava
city: Pilsen
country: Czech Republic
facility: University Hospital Pilsen
city: Prague
country: Czech Republic
facility: University Hospital Kralovske Vinohrady
city: Prague
country: Czech Republic
facility: General University Hospital Prague
Study officials:
affiliation: University Hospital Kralovske Vinohrady, Prague, Czech Republic
name: Heidi Mocikova, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: General University Hospital, Prague
name: Marek Trněný, prof.M.D.
role: STUDY_DIRECTOR
References: