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

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Unknown status
Phase
Phase 3
Locations
Czech Republic
Study Type
Interventional
Intervention
Methotrexate
Sponsored by
Czech Lymphoma Study Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diffuse Large B-cell Lymphoma focused on measuring Lymphoma, B cell, Central nervous system relapse, Methotrexate, Intrathecal chemotherapy

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Hospital Brno-BohuniceRecruiting
  • University Hospital Hradec KrálovéRecruiting
  • University Hospital OstravaRecruiting
  • University Hospital PilsenRecruiting
  • University Hospital Kralovske VinohradyRecruiting
  • General University Hospital PragueRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Arm A - Methotrexate i.v.

Arm B - Methotrexate i.t.

Arm C - no Methotrexate

Arm 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).

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).

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

Outcomes

Primary Outcome Measures

Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis

Secondary Outcome Measures

Complete remission rate
Overall response rate
Overall survival
Progression-free survival

Full Information

First Posted
May 12, 2016
Last Updated
June 3, 2016
Sponsor
Czech Lymphoma Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT02777736
Brief Title
CNS Prophylaxis in Diffuse Large B-cell Lymphoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
July 2015 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Czech Lymphoma Study Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
Lymphoma, B cell, Central nervous system relapse, Methotrexate, Intrathecal chemotherapy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A - Methotrexate i.v.
Arm Type
Experimental
Arm 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).
Arm Title
Arm B - Methotrexate i.t.
Arm Type
Active Comparator
Arm 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).
Arm Title
Arm C - no Methotrexate
Arm Type
No Intervention
Arm Description
Patients with 0-1 risk factor for CNS relapse will not receive CNS prophylaxis.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Methotrexate,manufactured by EBEWE, Methotrexate, manufactured by HOSPIRA
Intervention Description
i.v. or intrathecal CNS prophylaxis
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Complete remission rate
Time Frame
1 year
Title
Overall response rate
Time Frame
1 year
Title
Overall survival
Time Frame
2 years
Title
Progression-free survival
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heidi Mocikova, M.D., Ph.D.
Phone
+420267163554
Email
heidi.mocikova@fnkv.cz
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heidi Mocikova, M.D., Ph.D.
Organizational Affiliation
University Hospital Kralovske Vinohrady, Prague, Czech Republic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marek Trněný, prof.M.D.
Organizational Affiliation
General University Hospital, Prague
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital Brno-Bohunice
City
Brno
ZIP/Postal Code
62500
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Janikova, M.D.,Ph.D.
Facility Name
University Hospital Hradec Králové
City
Hradec Králové
ZIP/Postal Code
50005
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Belada, M.D., Ph.D.
Facility Name
University Hospital Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juraj Ďuraš, M.D.
Facility Name
University Hospital Pilsen
City
Pilsen
ZIP/Postal Code
304 60
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Pachner, M.D.
Facility Name
University Hospital Kralovske Vinohrady
City
Prague
ZIP/Postal Code
100 34
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heidi Mocikova, M.D., Ph.D.
Facility Name
General University Hospital Prague
City
Prague
ZIP/Postal Code
12808
Country
Czech Republic
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Pytlik, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.lymphoma.cz
Description
Official Site of the Czech Lymphoma Study Group
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://www.lymphoma.cz/docs/studies/dlbcl/CLSG-CNS-01_en.pdf

Learn more about this trial

CNS Prophylaxis in Diffuse Large B-cell Lymphoma

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