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

Central Nervous System Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011920
• Other study ID #: IELSG32
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2009
• Last updated: August 22, 2017
• Start date: November 2009
• Est. completion date: March 2017

Study information

• Verified date: July 2016
• Source: International Extranodal Lymphoma Study Group (IELSG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 + 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: March 2017
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Central Nervous System Lymphoma
• Lymphoma

Intervention

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.
• 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

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.

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

Other:
• APBSCT
Autologous peripheral blood stem cell transplant (APBSCT)

Locations

Country	Name	City	State
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
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
Switzerland	IOSI - Oncology Institute of Southern Switzerland	Bellinzona
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Queen's Hospital	Romford

Sponsors (1)

Lead Sponsor	Collaborator
International Extranodal Lymphoma Study Group (IELSG)

Countries where clinical trial is conducted

Germany,  Italy,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate after primary chemotherapy and 2 years failure free survival at second randomization		3 months, 2 years
Secondary	safety, as acute and long-term toxicity		Throughout all the active treatment period
Secondary	overall survival		From entry onto trial until death for any cause