An international phase II trial assessing tolerability and efficacy of two sequential chemotherapy regimens , followedby high stem cell transplant in patients with systemic B-cell lymphoma who have central nervous system involvementat diagnosis or relapse (MARIETTA regimen).
- Conditions
- Systemic B-cell lymphoma with central nervous system involvement.MedDRA version: 20.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003031-19-NL
- Lead Sponsor
- International Extranodal Lymphoma Study Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 76
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. 4. No previous treatment with
high-dose methotrexate-based chemotherapy and/or brain irradiation.
5. Age 18-70 years
6. ECOG performance status 0-3
7. Adequate bone marrow, renal and hepatic function 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. 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The principal research question is to evaluate the efficacy and feasibility of a new sequential treatment regimen for<br>patients who have diffuse large B-cell lymphoma with CNS involvement.;Secondary Objective: Other key objectives are to collect data on complete remission rates before stem cell transplant; response duration;<br>overall survival; and safety.;Primary end point(s): The primary end point of the study is 1-year progression-free survival (PFS).<br>PFS for all patients is defined as the interval between the time of entry onto trial and failure (relapsing or progressive disease), death from any cause or date of the last visit of follow-up.;Timepoint(s) of evaluation of this end point: After the 2nd, 4th and 6th courses of chemoimmunotherapy and 45 days<br>after ASCT (autologous stem cell transplantation). Then up to 12 months follow up.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Complete remission rate before autologous stem cell transplantation<br>• Response duration<br>• Overall survival (OS)<br>• Safety<br>;Timepoint(s) of evaluation of this end point: Complete remission rate before autologous stem cell transplantation.<br>Response duration: for all patients defined as the time from the first assessment that documents the response to the<br>date of relapse, date of death from any cause or date of the last visit of follow-up.<br>Overall survival (OS): for all patients, defined as the time from entry<br>into trial until death from any cause or date of the last visit of follow-up.<br>Patients will be followed up for 5 years.