Most patients being diagnosed with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) are 60 years or older. Elderly patients with PCNSL have a poor prognosis and there is a great medical need to improve outcome for this vulnerable population. In Germany and many international centres, there are currently two widely used strategies to treat elderly PCNSL patients who are eligible for high-dose methotrexate (HD-MTX) treatment, which have not yet been compared head-to-head. The R-MP regimen has been established by the Cooperative PCNSL Study Group as a "conventional" immunochemotherapy standard treatment for elderly patients with newly diagnosed disease and consists of Rituximab, HD-MTX and Procarbazine followed by maintenance therapy with Procarbazine. In contrast, another recently established protocol also includes HD-MTX-based induction therapy, but followed by consolidating high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT). This is an overall more intensive, but substantially shorter treatment approach, feasible for elderly patients being considered eligible for a more intensive treatment. The PRIMA-CNS trial aims to compare these two treatment approaches with respect to survival, response rates and toxicity.
Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system.
Age > 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial).
Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
Diagnostic sample obtained by stereotactic or surgical biopsy, cerebrospinal fluid (CSF) cytology examination or vitrectomy.
Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
Systemic lymphoma manifestation (outside the CNS).
Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord.
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.
Parallel
R-MP and Procarbazine maintenance
DrugFirstline systemic treatment with conventinal immunochemotherapy (3 cycles of Rituximab-MTX-Procarbazine) followed by Procarbazine maintenance
R-MTX/AraC (MARTA) induction followed by consolidating HCT-ASCT
DrugFirstline systemic treatment with age-adjusted MTX based induction (2 cycles of Rituximab-Methotrexate-Cytarabin) followed by consolidating aged-adapted high-dose chemotherapy and autologous stem cell transplantation
Progression free survival (PFS) between the 2 arms
PFS is defined as the time from randomization to disease progression or death of any cause, with censoring at the last date the patient was seen alive and free of disease progression
Overall survival (OS) between the 2 arms
OS is defined as time from randomization until death from any cause, with censoring at the last date the patient was seen alive
Event free survival (EFS) between the 2 arms
EFS, defined as time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first, with censoring at the last date the patient was seen event-free
Remission status after 2 cycles of rituximab-methotrexate-procarbazine (R-MP) (arm A)/2 cycles of R-MTX/cytarabine (AraC)
Remission status after 2 cycles of RMP (arm A) / 2 cycles of R-MTX/AraC will be determined at response assessment (RA) I in both arms and will be divided in complete remission (CR), unconfirmed complete remission (CRu), partial remission (PR), stable disease (SD), progressive disease(PD) according to international PCNSL collaborative group (IPCG) criteria
Remission status after 3 cycles of R-MP (arm A)/consolidating HCT-ASCT (arm B)
determined at response assessment (RA) II and will be divided in CR, CRu, PR, SD, PD according to IPCG criteria
Safety: Toxicity
Incidence of (Serious) adverse events ((S)AE) as assessed by CTCAE v5.0
Safety: Neurotoxicity
Results in the following neuropsychological tests: Montreal Cognitive Assessment (MoCA), Trail Making Test A and B, the Rey-Osterrieth-Complex-Figure-Test and a verbal fluency test, performed at screening, RA II / premature EOT and every 12 months during follow-up.
Unplanned hospital admissions
Defined as in-patient hospitalization due to SAE from date of informed consent form (ICF) signature until 30 days after ASCT or day 30 after last administration of IMP, whatever occurs first. Each hospitalization will be counted as a single event.
Length of hospital stays
Measured as number of nights in hospital due to SAE as defined above, i.e. hospital stays from date of ICF signature until 30 days after ASCT or day 30 after last administration of IMP, whatever occurs first.
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University Hospital Freiburg
Lead sponsor
German Federal Ministry of Education and Research
Collaborator
University Hospital Tuebingen
Collaborator
Heinrich-Heine University, Duesseldorf
Collaborator
Klinikum Stuttgart
Collaborator
University of Kaiserslautern
Collaborator
University Hospital Munich
Collaborator
University Hospital Regensburg
Collaborator
