NCT02329080

New Combination of Chemoimmunotherapy for Systemic B-cell Lymphoma With Central Nervous System Involvement

An International Phase II Trial Assessing Tolerability and Efficacy of Sequential Methotrexate-Aracytin-based Combination and R-ICE Combination, Followed by HD Chemotherapy Supported by ASCT, in Patients With Systemic B-cell Lymphoma With CNS Involvement at Diagnosis or Relapse (MARIETTA Regimen)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: International Extranodal Lymphoma Study Group (IELSG) · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is an open, non comparative, multicentre phase II trial, to evaluate the efficacy and feasibility of a new sequential combination of HD-MTX-AraC-based chemoimmunotherapy, followed by R-ICE regimen, and by high-dose chemotherapy supported by ASCT.

Detailed description

Treatment includes 6 courses of chemoimmunotherapy, the first three courses with an high dose methotrexate-based combination (MATRIX) followed by other three courses of R-ICE combination and finally a BCNU-thiotepa- containing conditioning and subsequent autologous stem cell transplantation. MATRIX (courses 1, 2, 3): Rituximab 375 mg/m2, Methotrexate 3.5 g/m2, Cytarabine 2 g/m2, Folinic rescue 15 mg/m2, Thiotepa 30 mg/m2, Intrathecal liposomial cytarabine 50 mg, rHuG-CSF 2,5 g/kg s.c. R-ICE (courses 4, 5, 6): Rituximab 375 mg/m2, Etoposide 100 mg/m2/d , Ifosfamide 5 g/m2, Intrathecal liposomial cytarabine 50 mg

Conditions

• Diffuse Large B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	Methotrexate	methotrexate 3.5 g/m2 on day 1 courses 1, 2,3 of MATRIX regimen
DRUG	Rituximab	Rituximab 375 mg/m2 as conventional IV infusion on day 0 courses 1, 2,3 (MATRIX regimen) and on day 1 courses 4,5,6 (R-ICE)
DRUG	Cytarabine	Cytarabine 2 g/m2 every 12 hours, in 3-hr infusion on days 2,3 courses 1, 2,3 (MATRIX regimen)
DRUG	Thiotepa	Thiotepa 30 mg/m2 in 30 minutes infusion on day 4 courses 1, 2,3 (MATRIX regimen) and 5 mg/kg in 250 ml of saline sol. in 2-hrs infusion every 12 hours on day -5 and -4 of conditioning and ASCT
DRUG	liposomial cytarabine	Intrathecal liposomial cytarabine 50 mg on day 5 courses 1, 2,3 (MATRIX regimen) and on day 4 courses 4,5,6 (R-ICE)
DRUG	Etoposide	Etoposide 100 mg/m2/d in 500 mL saline sol. in 30 minutes on day 1-2-3 courses 4,5,6 (R-ICE)
DRUG	Ifosfamide	Ifosfamide 5 g/m2 in 1.000 mL saline sol. in 24-hour infusion on day 2 courses 4,5,6 (R-ICE)
DRUG	Carmustine	BCNU (carmustine) 400 mg/m2 in 500 mL glucose 5% sol. in 1-hr infusion on day-6 of conditioning and ASCT
RADIATION	whole brain radiotherapy	whole-brain irradiation 36 Gy + tumor- bed boost 10 Gy in patients with residual disease in the parenchymal brain/cerebellum.

Timeline

• Start date: 2014-12-01
• Primary completion: 2019-08-01
• Completion: 2024-03-22
• First posted: 2014-12-31
• Last updated: 2025-07-08
• Results posted: 2025-07-08

Locations

36 sites across 4 countries: Czechia, Italy, Netherlands, United Kingdom