CNS Prophylaxis in Diffuse Large B-cell Lymphoma

Diffuse Large B-cell Lymphoma Clinical Trial

— CLSG-CNS-001  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02777736
• Other study ID #: CLSG-CNS-001
• Secondary ID: 2015-000591-97
• Status: Recruiting
• Phase: Phase 3
• First received: May 12, 2016
• Last updated: June 3, 2016
• Start date: July 2015
• Est. completion date: December 2019

Study information

• Verified date: June 2016
• Source: Czech Lymphoma Study Group
• Contact: Heidi Mocikova, M.D., Ph.D.
• Phone: +420267163554
• Email: heidi.mocikova[@]fnkv.cz
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Methotrexate
i.v. or intrathecal CNS prophylaxis

Locations

Country	Name	City	State
Czech Republic	University Hospital Brno-Bohunice	Brno
Czech Republic	University Hospital Hradec Králové	Hradec Králové
Czech Republic	University Hospital Ostrava	Ostrava
Czech Republic	University Hospital Pilsen	Pilsen
Czech Republic	General University Hospital Prague	Prague
Czech Republic	University Hospital Kralovske Vinohrady	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Czech Lymphoma Study Group

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis		1 year	Yes
Secondary	Complete remission rate		1 year	Yes
Secondary	Overall response rate		1 year	Yes
Secondary	Overall survival		2 years	Yes
Secondary	Progression-free survival		2 years	Yes

External Links

•   Official Site of the Czech Lymphoma Study Group