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Central Nervous System LymphomaPhase 2NCT01011920

Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma

A Phase 2 study testing Methotrexate, Ara-C and Rituximab in people with Central Nervous System Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 54 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter open label randomized phase II trial. Enrolled Primary Central Nervous System Lymphoma (PCNSL) patients will be stratified according to the IELSG score and randomized to receive one of the follows as primary chemotherapy: Arm A: Methotrexate (MTX) + Cytarabine (Ara-C) Arm B: MTX + Ara-C +… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Central Nervous System Lymphoma
What is being tested?
Methotrexate, Ara-C and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
227 participants
Where
54 sitesin 5 countries
Study dates
Nov 2009to 19 Dec 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological or cytological assessed diagnosis of non-Hodgkin's lymphoma.
  • Diagnostic sample obtained by stereotactic or surgical biopsy, Cerebrospinal Fluid (CSF) cytology examination or vitrectomy.
  • Disease exclusively localized into the central nervous system, CSF, cranial nerves or eyes.
  • At least one measurable lesion.
  • Previously untreated patients (previous or ongoing steroid therapy admitted).
  • Age 18-65 years (with ECOG Performance Status 0-3) or 66-70 (with ECOG Performance Status 0-2).
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  • Adequate bone marrow, renal, cardiac, and hepatic function.
  • Sexually active patients of childbearing potential agreeing in implementing adequate contraceptive measures during study participation.
  • Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Patient-signed informed consent obtained before registration.

Who cannot join

  • Patients with lymphomatous lesions outside the CNS.
  • Patients with a previous non-Hodgkin lymphoma at any time.
  • Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other cancers without evidence of disease at least from 5 years.
  • HBsAg and HCV positivity.
  • HIV infection, previous organ transplantation or other clinically evident form of immunodeficiency.
  • Concurrent treatment with other experimental drugs.
Show all 9Show fewer
  • Concurrent Pregnancy or lactation.
  • Patients not agreeing to take adequate contraceptive measures during the study.
  • Symptomatic coronary artery disease, cardiac arrhythmias uncontrolled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease).

Trial locations and contacts

54 sites in 5 countries.

54 sites in 5 countries

Italy24 sites

  • A.O. SS. Antonio e Biagio e Cesare Arrigo

    Alessandria

  • Istituto Tumori Giovanni Paolo II

    Bari

  • Ospedale Centrale di Bolzano

    Bolzano

  • Spedali Civili

    Brescia

  • Ospedale Businco

    Cagliari

  • San Raffaele H Scientific Institute

    Milan

  • Grande Ospedale Metropolitano Niguarda

    Milan

  • Istituto Nazionale Tumori, Fondazione G. Pascale

    Naples

  • Ospedale Umberto I

    Nocera Inferiore

  • Ospedale Civile S.Spirito

    Pescara

  • AOU Pisana

    Pisa

  • Ospedale delle Croci

    Ravenna

  • Arcispedale Santa Maria Nuova

    Reggio Emilia

  • Ospedale degli Infermi

    Rimini

  • Istituto Nazionale dei Tumori Regina Elena

    Roma

  • Università degli Studi La Sapienza

    Roma

  • Humanitas

    Rozzano

  • Casa Sollievo della Sofferenza

    San Giovanni Rotondo

  • Azienda Ospedaliera Universitaria Senese

    Siena

  • Azienda Ospedaliera Sanitaria Santa Maria

    Terni

  • Ospedale Maggiore S. Giovanni Battista

    Torino

  • Azienda Sanitaria Universitaria Friuli Centrale

    Udine

  • Policlinico G.B. Rossi

    Verona

  • ULSS 8 Berica - Ospedale S. Bortolo

    Vicenza

Other trials in Italy

Germany20 sites

  • University Hospital

    Aachen

  • Städtisches Klinikum

    Braunschweig

  • Klinikum Bremen-Mitte

    Bremen

  • Klinikum Chemnitz

    Chemnitz

  • Universitätsklinikum

    Cologne

  • Universitätsklinikum Erlangen

    Erlangen

  • "Klinik für Hämatologie Universitätsklinikum Essen"

    Essen

  • Klinikum der Johann-Wolfgang- Goethe-Universität

    Frankfurt am Main

  • Uniklinik Freiburg

    Freiburg im Breisgau

  • Klinikum der Justus-Liebig-Universität

    Giessen

  • Georg-August-Universität

    Göttingen

  • Universitätsklinikum Halle

    Halle

  • Universitätskrankenhaus Hamburg-Eppendorf

    Hamburg

  • SLK-Kliniken GmbH

    Heilbronn

  • Universitätsklinikum des Saarlandes

    Homburg/Saar

  • Friedrich Schiller Universitaet Jena

    Jena

  • Universitätsklinikum und Städtisches Krankenhaus

    Kiel

  • Johannes Gutenberg Universität Mainz

    Mainz

  • Technische Universität in München

    München

  • Universitätsklinikum Ulm

    Ulm

Other trials in Germany

United Kingdom6 sites

  • University Hospital Aintree

    Liverpool

  • University College Hospital

    London

  • The Christie Hospital NHS Foundation Trust

    Manchester

  • Nottingham City Hospital

    Nottingham

  • Queen's Hospital

    Romford

  • Medical Oncology Unit General Hospital

    Southampton

Other trials in United Kingdom

Denmark3 sites

  • University Hospital

    Aarhus

  • Rigshospitalet,

    Copenhagen

  • Herlev Hospital

    Herlev

Other trials in Denmark

Switzerland1 site

  • IOSI - Oncology Institute of Southern Switzerland

    Bellinzona, 6500

Other trials in Switzerland

About this study

Official title: Randomized Phase II Trial On Primary Chemotherapy With High-Dose Methotrexate And High-Dose Cytarabine With Or Without Thiotepa, And With Or Without Rituximab, Followed By Brain Irradiation Vs. High-Dose Chemotherapy Supported By Autologous Stem Cells Transplantation For Immunocompetent Patients With Newly Diagnosed Primary CNS Lymphoma

This is a multicenter open label randomized phase II trial.

Enrolled Primary Central Nervous System Lymphoma (PCNSL) patients will be stratified according to the IELSG score and randomized to receive one of the follows as primary chemotherapy:

Read more
  • Arm A: Methotrexate (MTX) + Cytarabine (Ara-C)
  • Arm B: MTX + Ara-C + rituximab
  • Arm C: MTX + Ara-C + rituximab + thiotepa.

Chemotherapy will be administered every three weeks. The maximum number of chemotherapy induction courses will be 4. Patients in Stable Disease (SD) or better after two courses will receive two more courses of the same primary chemotherapy regimen. Stem-cells harvest will be performed in the three arms after the second course. After 4 courses response assessment will be performed.

Patients who will not achieve SD or better after the 4th course, as well as those who will experience Progressive Disease (PD) at any time and those who will not achieve a sufficient stem cell harvest, will receive Whole Brain Radiation Therapy (WBRT) 36-40 Gy +/- tumor bed boost of 9 Gy.

Patients who will achieve SD or better after the 4th course will be stratified according to objective response to primary chemotherapy and to primary chemotherapy regimen and randomly allocated to receive as consolidation therapy one of the follows:

  • Arm D: WBRT 36 Gy +/- boost 9 Gy
  • Arm E: Carmustine (BCNU) + Thiotepa + Autologous Peripheral Blood Stem Cell Transplant (APBSCT) Patients in Complete Response (CR) after WBRT or APBSCT will remain in follow-up. Patients who will not achieve a CR after WBRT will be managed according to physician's preferences. Patients who will not achieve a CR after APBSCT will be referred to WBRT.
Being tested
Methotrexate, Ara-C, Rituximab, Thiotepa, radiotherapy
Keywords
newly diagnosed primary central nervous system lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion) on day 1, every 3 weeks for a maximum of 4 courses.

  • Ara-CDrug

    Also called Cytarabine

    Cytarabine 2 g/m2 (1 hr infusion, twice a day every 12 hours), on d 2 - 3 every 3 weeks for a maximum of 4 courses

  • RituximabDrug

    Also called MabThera

    Rituximab 375 mg/m2 conventional infusion on day - 5 \& 0 every 3 weeks for a maximum of 4 cycles

  • ThiotepaDrug

    ARM C: Thiotepa 30 mg/m2 (30 min. Infusion) on day 4 every 3 weeks for a maximum of 4 courses ARM E: Thiotepa 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs days -5 \& -4

  • radiotherapyRadiation

    Photons of 4-10 Mev, 180 cGy per day, 5 weekly fractions. Whole-brain will be irradiated by two opposite lateral fields including the first two cervical vertebras and the posterior two thirds of the orbits, which must be shielded after 30 Gy (after 36 Gy in the case of evident intraocular disease at diagnosis). Tumor-bed (boost or partial-brain RT) will be irradiated by 2 to 4 isocentric treatment fields based on tumor location, with all portals treated per each RT session.

  • BCNUDrug

    Also called Carmustine

    BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6

  • APBSCTOther

    Autologous peripheral blood stem cell transplant (APBSCT)

Study groups in NCT01011920
Study groupRoleWhat they receive
MTX + AraCExperimentalArm A Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion) d 1 Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3
Receives: Drug: Methotrexate; Drug: Ara-C
MTX + Ara-C + RituximabExperimentalArm B Rituximab 375 mg/m2 conventional infusion d -5 \& 0 Methotrexate 3.5 g/m2 0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion d 1 Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3
Receives: Drug: Methotrexate; Drug: Ara-C; Drug: Rituximab
MTX + Ara-C + rituximab+thiotepaExperimentalArm C Rituximab 375 mg/m2 conventional infusion d -5 \& 0 Methotrexate 3.5 g/m2 0.5 g/m2 in 15 min. + 3 g/m2 in 3-hr infusion d 1 Cytarabine 2 g/m2 1 hr infusion, twice a day (every 12 hs.) d 2 - 3 Thiotepa 30 mg/m2 30 min. Infusion d 4
Receives: Drug: Methotrexate; Drug: Ara-C; Drug: Rituximab; Drug: Thiotepa
WBRT 36 Gy +/- boost 9 GyExperimentalARM D: WBRT with 36 Gy in the case of CR to primary chemotherapy or the same WBRT dose followed by a tumor-bed boost of 9 Gy with 1-2 cm of margin surrounding enhanced residual lesion (total tumor-bed dose 45 Gy) in patients who achieved a PR or SD after primary chemotherapy. Photons of 4-10 Mev, 180 cGy per day, 5 weekly fractions.
Receives: Radiation: radiotherapy
BCNU + Thiotepa + APBSCTExperimentalArm E BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6 Thiotepa 5 mg/kg in 250 ml saline sol 2-hr inf. every 12 hrs days -5 \& -4 Reinfusion of PBSC ≥5 x 106 CD34+ cells/kg day 0
Receives: Drug: Thiotepa; Drug: BCNU; Other: APBSCT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Remission Rate After Primary Chemotherapy

    Percentage of patients with complete remission after 3 month of treatment. Percentage values are rounded to whole numbers.

    Measured: 3 months after treatment start

  2. 2 Years Failure Free Survival (FFS) After Second Randomization

    Percentage of patients alive and free from disease progression, relapse, need for new treatment, after 2 years from study entry. Percentage values are rounded to whole numbers.

    Measured: Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry

Secondary outcomes (2)

  1. 2 Years Failure Free Survival (FFS)

    Percentage of patients alive and free from disease progression, relapse, need for new treatment, after 2 years from study entry any cause. Percentage values are rounded to whole numbers.

    Measured: Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry

  2. 2 Year Overall Survival (OS)

    Percentage of patients alive after 2 years from study entry. Percentage values are rounded to whole numbers.

    Measured: From study entry until 2 years after

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionMar 2015
  4. Study completion19 Dec 2024

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
227 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01011920
Sponsor's protocol ID
IELSG32
Other IDs
2009-012432-32, 2009
Status last verified
Mar 2026
First submitted
9 Nov 2009
Last updated
19 Mar 2026
Data monitoring committee
Yes

Publications

  • Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosee P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sonderskov Gorlov J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. doi: 10.1016/S2352-3026(17)30174-6. Epub 2017 Oct 17.

    PubMed 29054815

  • Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosee PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Ruda R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gorlov JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. doi: 10.1016/S2352-3026(16)00036-3. Epub 2016 Apr 6.

    PubMed 27132696

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate, Ara-C and Rituximab in people with Central Nervous System Lymphoma, run by International Extranodal Lymphoma Study Group (IELSG) at 54 sites in 5 countries.

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 10 inclusion and 9 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: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in Italy, Germany, United Kingdom, Denmark, Switzerland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Remission Rate After Primary Chemotherapy (time frame: 3 months after treatment start). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01011920, which also lists 2 linked publications.

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 19 Mar 2026.

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