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

• Register: ClinicalTrials.gov
• Last refreshed on: 29 May 2023
• Main ID: NCT02329080
• Date of registration: 22/12/2014
• Prospective Registration: No
• Primary sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Public title: New Combination of Chemoimmunotherapy for Systemic B-cell Lymphoma With Central Nervous System Involvement
• Scientific title: 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)
• Date of first enrolment: December 2014
• Target sample size: 76
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02329080
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Czech Republic, Czechia, Italy, Netherlands, United Kingdom

Contacts

• Name: Andrés JM Ferreri, MD
• Affiliation: IELSG

Key inclusion & exclusion criteria

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

11. Female patients must be non-pregnant and non-lactating. Sexually active patients of
childbearing potential must implement adequate contraceptive measures during study
participation

12. No treatment with other experimental drugs within the 6 weeks previous to enrolment

13. Given written informed consent prior to any study specific procedures, with the
understanding that the patient has the right to withdraw from the study at any time,
without any prejudice. Informed consent signed by a patient's guardian is acceptable
if the patient is not able to decide inclusion in the study due to cognitive
impairment

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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diffuse Large B-cell Lymphoma

Intervention(s)

Radiation: whole brain radiotherapy

Drug: Ifosfamide

Drug: Cytarabine

Drug: liposomial cytarabine

Drug: Rituximab

Drug: Etoposide

Drug: Thiotepa

Drug: Carmustine

Drug: Methotrexate

Primary Outcome(s)

progression free survival [Time Frame: one year]

Secondary Outcome(s)

number of participants with adverse events [Time Frame: from time informed consent is given until 30 days after end of treatment]

overall survival [Time Frame: from entry onto trial until death from any cause or date of the last visit of follow-up (5 years)]

response duration [Time Frame: after the 2nd, 4th and 6th courses of chemoimmunotherapy and 45 days after ASCT. During follow up every 3 months for 2 years, than every 6 months for 3 years and yearly thereafter]

Complete remission rate [Time Frame: at the end of chemoimmunotherapy (up to 22-24 weeks from treatment start)]

Secondary ID(s)

IELSG42

Source(s) of Monetary Support

Please refer to primary and secondary sponsors