Trial for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma - Full Text View

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:

MedlinePlus related topics: Lymphoma

Drug Information available for: Thiotepa Methotrexate Cytarabine Methotrexate sodium Rituximab

Genetic and Rare Diseases Information Center resources: Central Nervous System Lymphoma, Primary Lymphosarcoma

U.S. FDA Resources

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 2016 (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

Locations


Germany
University Hospital
Aachen, Germany
Universitätsklinikum Erlangen
Erlangen, Germany
"Klinik für Hämatologie Universitätsklinikum Essen"
Essen, Germany
Uniklinik Freiburg
Freiburg, Germany
Universitätskrankenhaus Hamburg-Eppendorf
Hamburg, Germany
Friedrich Schiller Universitaet Jena
Jena, Germany
Johannes Gutenberg Universität Mainz
Mainz, Germany
Technische Universität in München
München, Germany
Universitätsklinikum Ulm
Ulm, Germany
Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Spedali Civili
Brescia, Italy
San Raffaele H Scientific Institute
Milan, Italy
Ospedale Umberto I
Nocera Inferiore, Italy
Ospedale Civile S.Spirito
Pescara, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia, Italy
Istituto Nazionale dei Tumori Regina Elena
Roma, Italy
Università degli Studi La Sapienza
Roma, Italy
Humanitas
Rozzano, Italy
Ospedale Maggiore S. Giovanni Battista
Torino, Italy
Policlinico G.B. Rossi
Verona, Italy
Switzerland
IOSI - Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, 6500
United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom
Queen's Hospital
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:	December 22, 2014
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:


Cytarabine Methotrexate Rituximab Thiotepa Abortifacient Agents Abortifacient Agents, Nonsteroidal Alkylating Agents Anti-Infective Agents Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antineoplastic Agents, Alkylating Antirheumatic Agents	Antiviral Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Physiological Effects of Drugs Reproductive Control Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015