Diffuse Large B-cell LymphomaPhase 3CLSG-CNS-001NCT02777736
CNS Prophylaxis in Diffuse Large B-cell Lymphoma
A Phase 3 study testing Methotrexate in people with Diffuse Large B-cell Lymphoma, run by Czech Lymphoma Study Group at 6 sites in Czechia.
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… Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 6 sitesCzechia
- Study dates
- Jul 2015to Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
6 sites in 1 country.
6 sites in 1 country
Czechia6 sites, 6 recruiting
- Recruiting
University Hospital Brno-Bohunice
Brno, 62500
Andrea Janikova, M.D.,Ph.D.
- Recruiting
University Hospital Hradec Králové
Hradec Králové, 50005
David Belada, M.D., Ph.D.
- Recruiting
University Hospital Ostrava
Ostrava, 708 52
Juraj Ďuraš, M.D.
- Recruiting
University Hospital Pilsen
Pilsen, 304 60
Martin Pachner, M.D.
- Recruiting
University Hospital Kralovske Vinohrady
Prague, 100 34
Heidi Mocikova, M.D., Ph.D.
- Recruiting
General University Hospital Prague
Prague, 12808
Robert Pytlik, M.D.
About this study
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
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).
Read the 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.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Methotrexate
- Keywords
- Lymphoma, B cell, Central nervous system relapse, Methotrexate, Intrathecal chemotherapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Also called Methotrexate,manufactured by EBEWE, Methotrexate, manufactured by HOSPIRA
i.v. or intrathecal CNS prophylaxis
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Methotrexate i.v. | Experimental | 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). Receives: Drug: Methotrexate |
| Arm B - Methotrexate i.t. | Active comparator | 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). Receives: Drug: Methotrexate |
| Arm C - no Methotrexate | No intervention | Patients with 0-1 risk factor for CNS relapse will not receive CNS prophylaxis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis
Measured: 1 year
Secondary outcomes (4)
Complete remission rate
Measured: 1 year
Overall response rate
Measured: 1 year
Overall survival
Measured: 2 years
Progression-free survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study startJul 2015
- Primary completionDec 2018 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Czech Lymphoma Study Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Heidi Mocikova, M.D., Ph.D., Principal investigator, University Hospital Kralovske Vinohrady, Prague, Czech RepublicMarek Trněný, prof.M.D., Study director, General University Hospital, Prague
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02777736
- Sponsor's protocol ID
- CLSG-CNS-001
- Other IDs
- 2015-000591-97, 2015
- Acronym
- CLSG-CNS-001
- Status last verified
- Jun 2016
- First submitted
- 12 May 2016
- Last updated
- 6 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02777736
- Acronym / sponsor ID
- CLSG-CNS-001 / CLSG-CNS-001
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Lymphoma, B cell, Central nervous system relapse, Methotrexate, Intrathecal chemotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Czech Lymphoma Study GroupUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 19 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A - Methotrexate i.v. | Experimental | Drug: MethotrexatePatients 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 B - Methotrexate i.t. | Active comparator | Drug: MethotrexatePatients 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 C - no Methotrexate | No intervention | –Patients with 0-1 risk factor for CNS relapse will not receive CNS prophylaxis. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateAlso: Methotrexate,manufactured by EBEWE, Methotrexate, manufactured by HOSPIRAi.v. or intrathecal CNS prophylaxis | Drug | Arm A - Methotrexate i.v., Arm B - Methotrexate i.t. |
Primary outcome
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
4 secondary outcomes
Complete remission rate
Time frame: 1 year
Overall response rate
Time frame: 1 year
Overall survival
Time frame: 2 years
Progression-free survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2016.
- Official Site of the Czech Lymphoma Study GroupLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Diffuse Large B-cell Lymphoma
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Enrolling by invitationObservational study
Leukapheresis for CAR or Adoptive Cell Therapy Manufacturing
Leukemia, Lymphoma
Active, not recruitingPhase 1
Copanlisib and Nivolumab in Treating Patients With Richter's Transformation or Transformed Indolent Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia, Diffuse Large B-Cell Lymphoma
Active, not recruitingPhase 1/2
Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
RecruitingObservational study
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
Hematologic Malignancy, Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heidi Mocikova, M.D., Ph.D. principal investigator
University Hospital Kralovske Vinohrady, Prague, Czech Republic
Marek Trněný, prof.M.D. study director
General University Hospital, Prague
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate in people with Diffuse Large B-cell Lymphoma, run by Czech Lymphoma Study Group at 6 sites in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Heidi Mocikova, M.D., Ph.D. (+420267163554, heidi.mocikova@fnkv.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2016; AzTrials last refreshed its copy on 30 Oct 2026.