Trial for Patients With Newly Diagnosed Primary Central N... | NCT01011920 | Trialant
NCT01011920
Sponsor
International Extranodal Lymphoma Study Group (IELSG)
Status
Completed
Last Update Posted
Mar 19, 2026Actual
Enrollment
227Actual
Phase
Phase 2
Conditions
Central Nervous System Lymphoma
Interventions
Methotrexate
Ara-C
Rituximab
Thiotepa
radiotherapy
BCNU
APBSCT
Countries
Denmark
Germany
Italy
Switzerland
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01011920
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
IELSG32
Secondary IDs
ID
Type
Description
Link
2009-012432-32
EudraCT Number
Brief Title
Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma
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
Acronym
Not provided
Organization
International Extranodal Lymphoma Study Group (IELSG)OTHER
Status Module
Record Verification Date
Mar 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 2009
Primary Completion Date
Mar 2015Actual
Completion Date
Dec 19, 2024Actual
First Submitted Date
Nov 9, 2009
First Submission Date that Met QC Criteria
Nov 10, 2009
First Posted Date
Nov 11, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 11, 2026
Results First Submitted that Met QC Criteria
Mar 18, 2026
Results First Posted Date
Mar 19, 2026Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 18, 2026
Last Update Posted Date
Mar 19, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
International Extranodal Lymphoma Study Group (IELSG)OTHER
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief 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 + 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.
Detailed Description
Not provided
Conditions Module
Conditions
Central Nervous System Lymphoma
Keywords
newly diagnosed primary central nervous system lymphoma
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
227Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
MTX + AraC
Experimental
Arm 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
Drug: Methotrexate
Drug: Ara-C
MTX + Ara-C + Rituximab
Experimental
Arm 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
Drug: Methotrexate
Drug: Ara-C
Drug: Rituximab
MTX + Ara-C + rituximab+thiotepa
Experimental
Arm 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
Drug: Methotrexate
Drug: Ara-C
Drug: Rituximab
Drug: Thiotepa
WBRT 36 Gy +/- boost 9 Gy
Experimental
ARM 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.
Radiation: radiotherapy
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Methotrexate
Drug
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.
MTX + Ara-C + Rituximab
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Complete Remission Rate After Primary Chemotherapy
Percentage of patients with complete remission after 3 month of treatment. Percentage values are rounded to whole numbers.
3 months after treatment start
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.
Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry
Secondary Outcomes
Measure
Description
Time Frame
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.
Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
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).
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.
Exclusion Criteria:
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.
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).
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.
At the end of first randomization 167 patients with responsive or stable disease were observed . Eighteen patients experienced PD before the second randomization, 12 were deemed unfit, and 15 had no harvest.
Consequently, 122 patients were eligible and assessable for second randomization. Four patients refused the second randomization, leaving 59 patients allocated to Arm D and 59 to Arm E.
Of these, five patients refused consolidation resulting in 113 patients proceeding
Recruitment Details
Two hundreds and twenty seven patients were enrolled and treated in the IELSG32 study.
Eight patients were excluded (five from arm B and three from arm C) because of misdiagnosis, systemic lymphoma, or concomitant cancer.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
MTX + AraC
Arm 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
Methotrexate: 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-C: 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
Periods
Title
Milestones
Reasons Not Completed
First Randomization
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
BCNU + Thiotepa + APBSCT
Experimental
Arm 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
Drug: Thiotepa
Drug: BCNU
Other: APBSCT
MTX + Ara-C + rituximab+thiotepa
MTX + AraC
Ara-C
Drug
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
MTX + Ara-C + Rituximab
MTX + Ara-C + rituximab+thiotepa
MTX + AraC
Cytarabine
Rituximab
Drug
Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
MTX + Ara-C + Rituximab
MTX + Ara-C + rituximab+thiotepa
MabThera
Thiotepa
Drug
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
BCNU + Thiotepa + APBSCT
MTX + Ara-C + rituximab+thiotepa
radiotherapy
Radiation
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.
WBRT 36 Gy +/- boost 9 Gy
BCNU
Drug
BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
Universitätsklinikum und Städtisches Krankenhaus
Kiel
Germany
Johannes Gutenberg Universität Mainz
Mainz
Germany
Technische Universität in München
München
Germany
Universitätsklinikum Ulm
Ulm
Germany
A.O. SS. Antonio e Biagio e Cesare Arrigo
Alessandria
Italy
Istituto Tumori Giovanni Paolo II
Bari
Italy
Ospedale Centrale di Bolzano
Bolzano
Italy
Spedali Civili
Brescia
Italy
Ospedale Businco
Cagliari
Italy
San Raffaele H Scientific Institute
Milan
Italy
Grande Ospedale Metropolitano Niguarda
Milan
Italy
Istituto Nazionale Tumori, Fondazione G. Pascale
Naples
Italy
Ospedale Umberto I
Nocera Inferiore
Italy
Ospedale Civile S.Spirito
Pescara
Italy
AOU Pisana
Pisa
Italy
Ospedale delle Croci
Ravenna
Italy
Arcispedale Santa Maria Nuova
Reggio Emilia
Italy
Ospedale degli Infermi
Rimini
Italy
Istituto Nazionale dei Tumori Regina Elena
Roma
Italy
Università degli Studi La Sapienza
Roma
Italy
Humanitas
Rozzano
Italy
Casa Sollievo della Sofferenza
San Giovanni Rotondo
Italy
Azienda Ospedaliera Universitaria Senese
Siena
Italy
Azienda Ospedaliera Sanitaria Santa Maria
Terni
Italy
Ospedale Maggiore S. Giovanni Battista
Torino
Italy
Azienda Sanitaria Universitaria Friuli Centrale
Udine
Italy
Policlinico G.B. Rossi
Verona
Italy
ULSS 8 Berica - Ospedale S. Bortolo
Vicenza
Italy
IOSI - Oncology Institute of Southern Switzerland
Bellinzona
6500
Switzerland
University Hospital Aintree
Liverpool
United Kingdom
University College Hospital
London
United Kingdom
The Christie Hospital NHS Foundation Trust
Manchester
United Kingdom
Nottingham City Hospital
Nottingham
United Kingdom
Queen's Hospital
Romford
United Kingdom
Medical Oncology Unit General Hospital
Southampton
United Kingdom
Derived
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.
FG001
MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
FG002
MTX + Ara-C + Rituximab+Thiotepa
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
FG003
WBRT 36 Gy +/- Boost 9 Gy
ARM 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.
radiotherapy: 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.
FG004
BCNU + Thiotepa + APBSCT
Arm 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
Thiotepa: 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
BCNU: BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
FG0000 subjectsAfter first randomization, patients were randomized to Arm D and Arm E
FG0010 subjectsAfter first randomization, patients were randomized to Arm D and Arm E
FG0020 subjectsAfter first randomization, patients were randomized to Arm D and Arm E
FG00355 subjects113 patients proceeded to second randomization. See Pre-assignment details
FG00458 subjects113 patients proceeded to second randomization. See Pre-assignment details
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00352 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
MTX + AraC
Arm 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
Methotrexate: 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-C: 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
BG001
MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
BG002
MTX + Ara-C + Rituximab+Thiotepa
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00075
BG00169
BG00275
BG003219
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Age, Continuous
Median
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG00058(50 to 64)
BG00157(53 to 63)
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00029
BG00125
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Denmark
Title
Measurements
BG0006
BG0010
BG002
Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability graded as follows:
0. Fully active, able to carry on all pre-disease performance without restriction;
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature;
Ambulatory and capable of all selfcare but unable to carry out any work activities;
Capable of only limited selfcare;
Completely disabled; totally confined to bed or chair;
International Extranodal Lymphoma Study Group (IELSG) risk score
IELSG risk score is a widely used, 5-point prognostic model for primary central nervous system lymphoma (PCNSL) that predicts overall survival (OS) based on age (>60), performance status (ECOG >1), high serum LDH, high CSF protein, and deep brain involvement.
Low risk: 80% 2 years OS; Intermediate risk: 48% 2 years OS; High risk: 15% 2 years OS.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Low Risk
BG00014
BG001
Intraocular disease
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Intraocular disease
BG0005
BG0011
BG002
Meningeal involvement
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Meningeal involvement
BG00011
BG00110
BG002
Multiple lesions
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Multiple lesions
BG00045
BG00140
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Complete Remission Rate After Primary Chemotherapy
Percentage of patients with complete remission after 3 month of treatment. Percentage values are rounded to whole numbers.
Posted
Number
95% Confidence Interval
Percentage of participants
3 months after treatment start
ID
Title
Description
OG000
Arm A / MTX + AraC
Arm 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
Methotrexate: 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-C: 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
OG001
Arm B / MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
OG002
Arm C / MTX + Ara-C + Rituximab+Thiotepa
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
Units
Counts
Participants
OG00075
OG00169
OG00275
Title
Denominators
Categories
Title
Measurements
OG00023(14 to 31)
OG00130(21 to 42)
OG00249(38 to 60)
Primary
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.
Posted
Number
95% Confidence Interval
Percentage of participants
Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry
ID
Title
Description
OG000
Arm D / WBRT 36 Gy +/- Boost 9 Gy
ARM 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.
radiotherapy: 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.
OG001
Arm E / BCNU + Thiotepa + APBSCT
Arm 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
Thiotepa: 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
BCNU: BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
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.
Posted
Number
99% Confidence Interval
percentage of participants
Every 3 weeks during treatment and every 3 months thereafter up to 2 years from study entry
ID
Title
Description
OG000
Arm A / MTX + AraC
Arm 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
Methotrexate: 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-C: 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
OG001
Arm B / MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Secondary
2 Year Overall Survival (OS)
Percentage of patients alive after 2 years from study entry. Percentage values are rounded to whole numbers.
Posted
Number
95% Confidence Interval
percentage of participants
From study entry until 2 years after
ID
Title
Description
OG000
Arm A / MTX + AraC
Arm 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
Methotrexate: 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-C: 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
OG001
Arm B / MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
OG002
Arm C / MTX + Ara-C + Rituximab+Thiotepa
Time Frame
The AE/SAE reporting period began with the signing of the informed consent and ended 30 days after the last dose of the study drug (4 months). Deaths occurring later were only to be considered as SAE if they are related to the protocol treatments and had occurred within 6 months after the last dose.
Description
All AEs/SAEs that occurred in patients during the reporting period had to be reported to the Sponsor, regardless of whether the event was considered to be related to the study medication or not. In addition, any known SAE suspected to be related to the study treatment that occurred after the defined reporting period had to be reported to the Sponsor. All cause mortality was assessed through 10 years after study entry.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Arm A / MTX + AraC
Arm 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
Methotrexate: 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-C: 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
56
75
39
75
75
75
EG001
Arm B / MTX + Ara-C + Rituximab
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
41
69
38
69
68
69
EG002
Arm C / MTX + Ara-C + Rituximab+Thiotepa
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
33
75
39
75
74
75
EG003
Arm D / WBRT 36 Gy +/- Boost 9 Gy
ARM 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.
radiotherapy: 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.
30
55
5
55
38
55
EG004
Arm E / BCNU + Thiotepa + APBSCT
Arm 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
Thiotepa: 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
BCNU: BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
International Extranodal Lymphoma Study Group (IELSG)
+41 58 666
7321
ielsg@ior.usi.ch
ID
Term
D008727
Methotrexate
D003561
Cytarabine
D000069283
Rituximab
D013852
Thiotepa
D011878
Radiotherapy
D002330
Carmustine
Ancestor Terms
ID
Term
D000630
Aminopterin
D011622
Pterins
D011621
Pteridines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D006571
Heterocyclic Compounds
D003562
Cytidine
D011741
Pyrimidine Nucleosides
D011743
Pyrimidines
D006573
Heterocyclic Compounds, 1-Ring
D001087
Arabinonucleosides
D009705
Nucleosides
D009706
Nucleic Acids, Nucleotides, and Nucleosides
D058846
Antibodies, Monoclonal, Murine-Derived
D000911
Antibodies, Monoclonal
D000906
Antibodies
D007136
Immunoglobulins
D007162
Immunoproteins
D001798
Blood Proteins
D011506
Proteins
D000602
Amino Acids, Peptides, and Proteins
D012712
Serum Globulins
D005916
Globulins
D063088
Phosphoramides
D009943
Organophosphorus Compounds
D009930
Organic Chemicals
D013721
Triethylenephosphoramide
D001388
Aziridines
D001389
Azirines
D013812
Therapeutics
D009607
Nitrosourea Compounds
D014508
Urea
D000577
Amides
D009603
Nitroso Compounds
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
54 subjects
4 subjects
0 subjects
FG0042 subjects
Progressive Disease
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG0042 subjects
0
Between 18 and 65 years
BG00075
BG00169
BG00275
BG003219
>=65 years
BG0000
BG0010
BG0020
BG0030
57
(53 to 62)
BG00357(50 to 64)
29
BG00383
Male
BG00046
BG00144
BG00246
BG003136
5
BG00311
Italy
Title
Measurements
BG00029
BG00129
BG00234
BG00392
United Kingdom
Title
Measurements
BG0007
BG00118
BG00214
BG00339
Switzerland
Title
Measurements
BG0001
BG0011
BG0020
BG0032
Germany
Title
Measurements
BG00032
BG00121
BG00222
BG00375
46
BG00251
BG003145
ECOG>1
Title
Measurements
BG00027
BG00123
BG00224
BG00374
25
BG00388
No increased LDH
BG00038
BG00143
BG00250
BG003131
64
BG003174
No deep lesions
BG00017
BG00117
BG00211
BG00345
35
BG003101
No increased CSF protein
BG00023
BG00120
BG00218
BG00361
Not recorded
BG00019
BG00116
BG00222
BG00357
12
BG00213
BG00339
Intermediate Risk
BG00047
BG00144
BG00247
BG003138
High Risk
BG00014
BG00113
BG00215
BG00342
1
BG0037
No intraocular disease
BG00070
BG00168
BG00274
BG003212
13
BG00334
No meningeal involvement
BG00045
BG00143
BG00240
BG003128
Not recorded
BG00019
BG00116
BG00222
BG00357
41
BG003126
No multiple lesions
BG00030
BG00129
BG00234
BG00393
Units
Counts
Participants
OG00055
OG00158
Title
Denominators
Categories
Title
Measurements
OG00076(65 to 87)
OG00175(64 to 86)
OG002
Arm C / MTX + Ara-C + Rituximab+Thiotepa
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
Units
Counts
Participants
OG00075
OG00169
OG00275
Title
Denominators
Categories
Title
Measurements
OG00036(31 to 41)
OG00146(40 to 52)
OG00261(55 to 67)
Arm 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
Methotrexate: 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-C: 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
Rituximab: Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Thiotepa: 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
OG003
Arm D / WBRT 36 Gy +/- Boost 9 Gy
ARM 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.
radiotherapy: 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.
OG004
Arm E / BCNU + Thiotepa + APBSCT
Arm 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
Thiotepa: 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
BCNU: BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6