CNS Prophylaxis in Diffuse Large B-cell Lymphoma

NCT ID: NCT02777736

Last Updated: 2016-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Diffuse Large B-cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Arm A - Methotrexate i.v.

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).

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

i.v. or intrathecal CNS prophylaxis

Arm B - Methotrexate i.t.

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).

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

i.v. or intrathecal CNS prophylaxis

Arm C - no Methotrexate

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Methotrexate

i.v. or intrathecal CNS prophylaxis

Intervention Type DRUG

Other Intervention Names

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Methotrexate,manufactured by EBEWE Methotrexate, manufactured by HOSPIRA

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

72 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Czech Lymphoma Study Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Heidi Mocikova, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Kralovske Vinohrady, Prague, Czech Republic

Marek Trněný, prof.M.D.

Role: STUDY_DIRECTOR

General University Hospital, Prague

Locations

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University Hospital Brno-Bohunice

Brno, , Czechia

Site Status RECRUITING

University Hospital Hradec Králové

Hradec Králové, , Czechia

Site Status RECRUITING

University Hospital Ostrava

Ostrava, , Czechia

Site Status RECRUITING

University Hospital Pilsen

Pilsen, , Czechia

Site Status RECRUITING

University Hospital Kralovske Vinohrady

Prague, , Czechia

Site Status RECRUITING

General University Hospital Prague

Prague, , Czechia

Site Status RECRUITING

Countries

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Czechia

Central Contacts

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Heidi Mocikova, M.D., Ph.D.

Role: CONTACT

+420267163554

Facility Contacts

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Andrea Janikova, M.D.,Ph.D.

Role: primary

David Belada, M.D., Ph.D.

Role: primary

Juraj Ďuraš, M.D.

Role: primary

Martin Pachner, M.D.

Role: primary

Heidi Mocikova, M.D., Ph.D.

Role: primary

Robert Pytlik, M.D.

Role: primary

Study Documents

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Document Type: Study Protocol

View Document

Related Links

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http://www.lymphoma.cz

Official Site of the Czech Lymphoma Study Group

Other Identifiers

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2015-000591-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLSG-CNS-001

Identifier Type: -

Identifier Source: org_study_id

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