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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by International Extranodal Lymphoma Study Group (IELSG)
Sponsor:
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier:
NCT01011920
First received: November 9, 2009
Last updated: November 22, 2013
Last verified: March 2013
  Purpose

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.

Condition Intervention Phase
Central Nervous System Lymphoma
Drug: Methotrexate
Drug: Ara-C
Drug: Rituximab
Drug: Thiotepa
Radiation: radiotherapy
Drug: BCNU
Other: APBSCT
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by International Extranodal Lymphoma Study Group (IELSG):

Primary Outcome Measures:
  • response rate after primary chemotherapy and 2 years failure free survival at second randomization [ Time Frame: 3 months, 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • safety, as acute and long-term toxicity [ Time Frame: Throughout all the active treatment period ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: From entry onto trial until death for any cause ] [ Designated as safety issue: No ]

Estimated Enrollment: 126
Study Start Date: November 2009
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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.
Drug: 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
Other Name: Cytarabine
Experimental: 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
Drug: 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
Other Name: Cytarabine
Drug: Rituximab
Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Other Name: MabThera
Experimental: 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
Drug: 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
Other Name: Cytarabine
Drug: Rituximab
Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
Other Name: MabThera
Drug: 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
Experimental: 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.
Radiation: 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.
Experimental: 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
Drug: 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
Drug: BCNU
BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
Other Name: Carmustine
Other: APBSCT
Autologous peripheral blood stem cell transplant (APBSCT)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011920

Contacts
Contact: Emanuele Zucca, MD ++41918119040 ielsg@ticino.com

Locations
Germany
University Hospital Recruiting
Aachen, Germany
Contact: Jens Panse, MD         
Principal Investigator: Jens Panse, MD         
Universitätsklinikum Erlangen Recruiting
Erlangen, Germany
Contact: Stefan Krause, MD         
"Klinik für Hämatologie Universitätsklinikum Essen" Recruiting
Essen, Germany
Contact: Alexander Röth, MD         
Uniklinik Freiburg Recruiting
Freiburg, Germany
Contact: Gerald Illerhaus         
Universitätskrankenhaus Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: Stefan Balabanov, MD         
Friedrich Schiller Universitaet Jena Recruiting
Jena, Germany
Contact: Paul La Rosee, MD         
Principal Investigator: Paul La Rosee, MD         
Johannes Gutenberg Universität Mainz Recruiting
Mainz, Germany
Contact: G. Hess, MD         
Technische Universität in München Recruiting
München, Germany
Contact: N. von Bubnoff, MD         
Universitätsklinikum Ulm Recruiting
Ulm, Germany
Contact: Stephan Stilgenbauer, MD         
Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo Recruiting
Alessandria, Italy
Contact: Flavia Salvi, MD         
Spedali Civili Recruiting
Brescia, Italy
Contact: Alessandra Tucci         
Principal Investigator: Alessandra Tucci, MD         
San Raffaele H Scientific Institute Recruiting
Milan, Italy
Contact: Andres Ferreri, MD       ferreri.andres@hsr.it   
Principal Investigator: Andrés JM Ferreri, MD         
Ospedale Umberto I Recruiting
Nocera Inferiore, Italy
Contact: Alfonso D'Arco, MD         
Ospedale Civile S.Spirito Recruiting
Pescara, Italy
Contact: Giuseppe Fioritoni, MD         
Arcispedale Santa Maria Nuova Recruiting
Reggio Emilia, Italy
Istituto Nazionale dei Tumori Regina Elena Recruiting
Roma, Italy
Contact: Francesco Pisani, MD         
Università degli Studi La Sapienza Recruiting
Roma, Italy
Contact: Maurizio Martelli, MD         
Humanitas Recruiting
Rozzano, Italy
Contact: Monica Balzarotti         
Ospedale Maggiore S. Giovanni Battista Recruiting
Torino, Italy
Principal Investigator: Riccardo Soffietti, MD         
Policlinico G.B. Rossi Recruiting
Verona, Italy
Contact: Achille Ambrosetti         
Principal Investigator: Achille Ambrosetti, MD         
Switzerland
IOSI - Oncology Institute of Southern Switzerland Recruiting
Bellinzona, Switzerland, 6500
Contact: Emanuele Zucca, MD    +41918119040    ielsg@ticino.com   
Principal Investigator: Emanuele Zucca, MD         
United Kingdom
Nottingham City Hospital Recruiting
Nottingham, United Kingdom
Queen's Hospital Recruiting
Romford, United Kingdom
Sponsors and Collaborators
International Extranodal Lymphoma Study Group (IELSG)
Investigators
Study Chair: Andrés JM Ferreri, MD San Raffaele H Scientific Institute, Milan, Italy
Study Chair: Gerald Illerhaus, MD University Medical Center, Freiburg, Germany
Principal Investigator: Emanuele Zucca, MD IOSI, Bellinzona, Switzerland
  More Information

No publications provided

Responsible Party: International Extranodal Lymphoma Study Group (IELSG)
ClinicalTrials.gov Identifier: NCT01011920     History of Changes
Other Study ID Numbers: IELSG32
Study First Received: November 9, 2009
Last Updated: November 22, 2013
Health Authority: Switzerland: Swissmedic
Italy: Ethics Committee
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by International Extranodal Lymphoma Study Group (IELSG):
newly diagnosed primary central nervous system lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Thiotepa
Cytarabine
Methotrexate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 30, 2014