Overview

This trial is active, not recruiting.

Condition central nervous system lymphoma
Treatments methotrexate, ara-c, rituximab, thiotepa, radiotherapy, bcnu, apbsct
Phase phase 2
Target CD20
Sponsor International Extranodal Lymphoma Study Group (IELSG)
Start date November 2009
End date December 2016
Trial size 126 participants
Trial identifier NCT01011920, IELSG32

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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
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
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
(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
ara-c Cytarabine
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 MabThera
Rituximab 375 mg/m2 conventional infusion on day - 5 & 0 every 3 weeks for a maximum of 4 cycles
(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
ara-c Cytarabine
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 MabThera
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
(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.
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)
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 Carmustine
BCNU 400 mg/m2 in 500 ml saline sol 1-hr inf. day -6
apbsct
Autologous peripheral blood stem cell transplant (APBSCT)

Primary Outcomes

Measure
response rate after primary chemotherapy and 2 years failure free survival at second randomization
time frame: 3 months, 2 years

Secondary Outcomes

Measure
safety, as acute and long-term toxicity
time frame: Throughout all the active treatment period
overall survival
time frame: From entry onto trial until death for any cause

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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).

Additional Information

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
Principal investigator Emanuele Zucca, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by International Extranodal Lymphoma Study Group (IELSG).