Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. Considering the poor prognosis of this patient population, this randomised phase III trial proposal is of great clinical importance to provide patients optimal treatment.
Conditions
Sponsors
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system. 2. Age > 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial). 3. Histologically or cytologically assessed diagnosis of B -cell lymphoma by local pathologist. 4. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. 5. Disease exclusively located in the CNS. 6. At least 1 measurable lesion. 7. ECOG-Performance Status =2. 8. Patients possibly eligible for HCT-ASCT as judged by the treating physician. 9. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease. Additional randomization criteria: 1. Patients eligible for HCT-ASCT defined by the EBL score (at most 1 of the 3 following conditions may apply: ECOG PS > 1, Barthel Index of ADL 3), improvement of PS after pre-phase treatment or clinical judgement by the treating physician after discussion with the study expert team. 2. No evidence of disease progression after pre-phase treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 310
Exclusion criteria
Exclusion criteria: 1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation. 2. Systemic lymphoma manifestation (outside the CNS). 3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord. 4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ or other kinds of cancer without evidence of disease for at least 5 years. 5. Previous systemic Non-Hodgkin lymphoma at any time. 6. Inadequate renal function (creatinine clearance <60 ml/min). 7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision. 8. Active hepatitis B or C disease. 9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with administration of study medication within the last 30 days before the start of this study. 10. Clinically relevant third space fluid accumulation according to the investigator’s discretion. 11. Hypersensitivity to study treatment or any component of the formulation. 12. Taking any medications likely to cause interactions with the study medication. 13. Known or persistent abuse of medication, drugs or alcohol. 14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic. 15. Patients without legal capacity and who are unable to understand the nature, significance and consequences of the study and without designated legal representative. 16. Previous participation in this trial. 17. Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator. 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 19. Fertile patients refusing to use safe contraceptive methods during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary: To demonstrate that intensified chemotherapy followed by consolidating high-dose chemotherapy and autologous stem-cell transplantation (HCT-ASCT) is superior to conventional chemotherapy with R-MP followed by maintenance in elderly patients with newly diagnosed PCNSL in terms of progression free survival (PFS). Secondary: To compare quality of life, remission after induction treatment, remission after maintenance treatment (arm A) / consolidation treatment (arm B), event free survival, overall survival and treatment related morbidities (neurotoxicity and adverse events) between both treatment arms.;Secondary Objective: Secondary: To compare quality of life, remission after induction treatment, remission after maintenance treatment (arm A) / consolidation treatment (arm B), event free survival, overall survival and treatment related morbidities (neurotoxicity and adverse events) between both treatment arms.;Primary end point(s): Progression free survivalPFS;Timepoint(s) of evaluation of this end point: Progression free survival PFS - defined as the time from randomizationto disease progression or death of any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival (OS) • Event free survival (EFS; defined as time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first) • Remission during and after induction treatment • Remission after maintenance: 6 months after RAII • Quality of life (QoL): EORTC QLQ-C30, EORTC QLQ-BN20; measured during screening period, at RAII and premature EOT visit and thereafter every 12 months during follow-up. ;Timepoint(s) of evaluation of this end point: - Overall survival defined as time from randomization until death from any cause - event free survival defined as time from randomization to premature EOT due to any reason - Remission status after 2 cycles of R-MP (arm A) / 2 cycles of R-MTX / AraC will be determined at response assessment (RA) I in both arms - Remission status after completion of 3 cycles R-MP (arm A) / consolidating HDCT-ASCT (arm B) will be determined at RA II - Remission status after completion of maintenance treatment (armA)/6 months of FU (arm B) will be determined 6 months after RA II - EORTC at screening, at RA II/premature EOT + thereafter every 12 months during FU | — |
Countries
Austria, Germany
Contacts
Public ContactDepartment for Medicine I
Medical Center - University of Freiburg
Outcome results
None listed