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

June 3, 2016 updated by: Czech Lymphoma Study Group

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

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Czech Republic
      • Brno, Czech Republic, 62500
        • Recruiting
        • University Hospital Brno-Bohunice
        • Contact:
          • Andrea Janikova, M.D.,Ph.D.
      • Hradec Králové, Czech Republic, 50005
        • Recruiting
        • University hospital Hradec Králové
        • Contact:
          • David Belada, M.D., Ph.D.
      • Ostrava, Czech Republic, 708 52
        • Recruiting
        • University Hospital Ostrava
        • Contact:
          • Juraj Ďuraš, M.D.
      • Pilsen, Czech Republic, 304 60
        • Recruiting
        • University Hospital Pilsen
        • Contact:
          • Martin Pachner, M.D.
      • Prague, Czech Republic, 100 34
        • Recruiting
        • University Hospital Kralovske Vinohrady
        • Contact:
          • Heidi Mocikova, M.D., Ph.D.
      • Prague, Czech Republic, 12808
        • Recruiting
        • General University Hospital Prague
        • Contact:
          • Robert Pytlik, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: Methotrexate
i.v. or intrathecal CNS prophylaxis
Other Names:
  • Methotrexate,manufactured by EBEWE
  • Methotrexate, manufactured by HOSPIRA
Active Comparator: 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).
Drug: Methotrexate
i.v. or intrathecal CNS prophylaxis
Other Names:
  • Methotrexate,manufactured by EBEWE
  • Methotrexate, manufactured by HOSPIRA
No Intervention: Arm C - no Methotrexate
Patients with 0-1 risk factor for CNS relapse will not receive CNS prophylaxis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years
Progression-free survival
Time Frame: 2 years
2 years
Overall response rate
Time Frame: 1 year
1 year
Complete remission rate
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Czech Lymphoma Study Group

Investigators

  • Principal Investigator: Heidi Mocikova, M.D., Ph.D., University Hospital Kralovske Vinohrady, Prague, Czech Republic
  • Study Director: Marek Trněný, prof.M.D., General University Hospital, Prague

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

May 12, 2016

First Submitted That Met QC Criteria

May 17, 2016

First Posted (Estimate)

May 19, 2016

Study Record Updates

Last Update Posted (Estimate)

June 6, 2016

Last Update Submitted That Met QC Criteria

June 3, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLSG-CNS-001
  • 2015-000591-97 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Study Data/Documents

  1. Study Protocol

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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