CNS Prophylaxis in Diffuse Large B-cell Lymphoma (CLSG-CNS-001)

Czech Lymphoma Study Group

Status and phase: Unknown; Phase 3

Conditions: Diffuse Large B-cell Lymphoma

Treatments: Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT02777736

CLSG-CNS-001

2015-000591-97 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18 to 72 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 3 patient groups

Arm A - Methotrexate i.v.

Experimental group

Description:

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).

Treatment:

Drug: Methotrexate

Arm B - Methotrexate i.t.

Active Comparator group

Description:

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).

Treatment:

Drug: Methotrexate

Arm C - no Methotrexate

No Intervention group

Description:

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