Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma
- Conditions
- Central Nervous System Lymphoma
- Interventions
- Radiation: radiotherapyOther: APBSCT
- Registration Number
- NCT01011920
- Lead Sponsor
- International Extranodal Lymphoma Study Group (IELSG)
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 126
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MTX+ AraC Ara-C 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 Ara-C +Rituximab Ara-C 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 Ara-C +Rituximab 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 BCNU + Thiotepa + APBSCT 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 MTX+ AraC Methotrexate 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 WBRT 36 Gy +/- boost 9 Gy radiotherapy 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. Ara-C + rituximab+thiotepa Rituximab 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 Ara-C + rituximab+thiotepa Ara-C 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 Ara-C + rituximab+thiotepa 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 BCNU + Thiotepa + APBSCT BCNU 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 BCNU + Thiotepa + APBSCT Thiotepa 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
- Primary Outcome Measures
Name Time Method response rate after primary chemotherapy and 2 years failure free survival at second randomization 3 months, 2 years
- Secondary Outcome Measures
Name Time Method safety, as acute and long-term toxicity Throughout all the active treatment period overall survival From entry onto trial until death for any cause
Trial Locations
- Locations (23)
IOSI - Oncology Institute of Southern Switzerland
🇨🇭Bellinzona, Switzerland
A.O. SS. Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Uniklinik Freiburg
🇩🇪Freiburg, Germany
Friedrich Schiller Universitaet Jena
🇩🇪Jena, Germany
"Klinik für Hämatologie Universitätsklinikum Essen"
🇩🇪Essen, Germany
Universitätskrankenhaus Hamburg-Eppendorf
🇩🇪Hamburg, Germany
University Hospital
🇩🇪Aachen, Germany
Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Policlinico G.B. Rossi
🇮🇹Verona, Italy
Queen's Hospital
🇬🇧Romford, United Kingdom
Ospedale Civile S.Spirito
🇮🇹Pescara, Italy
San Raffaele H Scientific Institute
🇮🇹Milan, Italy
Spedali Civili
🇮🇹Brescia, Italy
Technische Universität in München
🇩🇪München, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Ospedale Umberto I
🇮🇹Nocera Inferiore, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Università degli Studi La Sapienza
🇮🇹Roma, Italy
Istituto Nazionale dei Tumori Regina Elena
🇮🇹Roma, Italy
Humanitas
🇮🇹Rozzano, Italy
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Ospedale Maggiore S. Giovanni Battista
🇮🇹Torino, Italy