Loading clinical trials...

COMPLETEDPHASE2

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)

NCT02329080•International Extranodal Lymphoma Study Group (IELSG)

View on ClinicalTrials.gov

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

Eligibility

Age

18 - 70 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically confirmed diagnosis of diffuse large B-cell lymphoma
•2. CNS involvement (brain, meninges, cranial nerves, eyes and/or spinal cord) at diagnosis (concomitant to extra-CNS disease) or relapse after conventional chemo(-immuno)therapy
•3. Diagnosis of CNS involvement either by brain biopsy or CSF cytology examination. Neuroimaging alone is acceptable when stereotactic biopsy is formally contraindicated or when the disease has been previously histologically documented in other areas and the CNS localization is concomitant with a diffuse progression of systemic disease.
•4. No previous treatment with high-dose methotrexate-based chemotherapy and/or brain irradiation. One-two courses of R-CHOP combination as upfront therapy are admitted in patients with large amount and/or extensive extra-CNS disease that could condition prognosis in an early phase of treatment. Local investigator decides if initial R-CHOP is needed based on patient's conditions
•5. Age 18-70 years
•6. ECOG performance status 0-3
•7. Adequate bone marrow (Platelets count ≥100.000/mm3, hemoglobin ≥9 g/dL, neutrophils count≥1.500/mm3), renal (creatinine clearance ≥60 mL/min), cardiac (LVEF ≥50%), and hepatic function (total serum bilirubine ≤3 mg/dL, AST/ALT and GGT ≤2.5 per upper normal limit value), unless the abnormality is due to lymphoma infiltration
•8. Absence of HIV infection and of detectable HCV-RNA and/or HBsAg and/or HBV-DNA
•9. No concurrent malignancies. Previous malignancies are accepted if surgically cured or if there was no evidence of disease in the last 3 years at a regular follow-up
•10. Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
+3 more criteria

Exclusion Criteria

•1. Other lymphoma categories other than diffuse large B-cell lymphoma. In particular, patients with primary mediastinal lymphoma, intravascular large B-cell lymphoma or leg-type large B-cell lymphoma are excluded.
•2. Patients with positive flow cytometry examination of the CSF, but negative results in CSF conventional cytology, and without any other evidence of CNS disease.
•3. Patients with exclusive CNS disease at presentation (primary CNS lymphoma) are excluded
•4. Previous treatment with support of autologous or allogeneic stem cells/bone marrow transplantation.
•5. Symptomatic coronary artery disease, cardiac arrhythmias not well controlled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
•6. Any other serious medical condition which could impair the ability of the patient to participate in the trial.

Locations (36)

Facultni nemocnice

Brno, Czechia

FNKV (Facultni Nemocnice Kralovske Vinohrady)

Prague, Czechia

Vseobecna facultni nemocnice v Praze

Prague, Czechia

Spedali Civili

Brescia, Italy

UO Ematologia e CTMO, PO Businco

Cagliari, Italy

IRST Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

UO Ematoliga Ospedale dell'Angelo

Mestre, Italy

San Raffaele H Scientific Institute

Milan, Italy

Istituto Nazionale Tumori

Milan, Italy

Ospedale Maggiore Policlinico

Milan, Italy

Key Dates

Start Date

December 1, 2014

Primary Completion Date

August 1, 2019

Completion Date

March 22, 2024

Last Updated

July 8, 2025

Enrollment

ACTUAL participants

Conditions

Diffuse Large B-cell Lymphoma

Interventions

Methotrexate

DRUG

Rituximab

DRUG

Cytarabine

DRUG

Thiotepa

DRUG

liposomial cytarabine

DRUG

Etoposide

DRUG

Ifosfamide

DRUG

Carmustine

DRUG

whole brain radiotherapy

RADIATION

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

NCT05139017

DLBCLDiffuse Large B-Cell Lymphoma

View study

RECRUITINGPHASE3

A Long-term Extension Study of PCI-32765 (Ibrutinib)

NCT01804686

Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma+5 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 8, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

A Long-term Extension Study of PCI-32765 (Ibrutinib)

Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid in Combination With Polatuzumab (ViPOR-P) in Relapsed/Refractory B-cell Lymphoma

Long-term Follow up Local Registry Study of Kymriah in South Korea

Registry Platform Hematologic Malignancies (RUBIN) - Extension of Tumor Registry Lymphatic Neoplasms