IELSG-45: Randomized Phase II Trial on Fitness- and Comorbidity- Tailored Treatment in Elderly Patients with Newly Diagnosed Primary CNS Lymphoma (FIORELLA Trial)
Primary central nervous system lymphomas (PCNSL) are rare aggressive
malignancies, mostly of B-cell origin, representing 4% of
intracranial neoplasms and 4-6% of extranodal non-Hodgkin's
lymphomas (NHL). Despite improvements in treat-ment, PCNSL is
associated with an aggressive course and un-satisfactory outcome.
The median age at diagnosis is 61 years and age over 60 years has
been reported to be an independent factor for a poorer outcome.
The modern treatment of PCNSL includes two phases: induc-tion and consolidation. The induction phase usually consists of a polychemotherapy combination, including high-dose metho-trexate as a critical drug, while there are at least four different strategies that can be used as consolidation: whole-brain irra-diation, myeloblative chemotherapy supported by autologous stem-cell transplantation, non- myeloblative chemotherapy, observation (only in patients who achieve complete remission after induction).
The feasibility of this overall strategy is limited, for several rea-sons, in elderly patients with newly diagnosed PCNSL. High-doses of antimetabolite-based chemotherapy, the standard induction for patients younger than 70 years, is often not feasi-ble in elderly patients. Among maintenance strategies, simple observation results in unacceptably high relapse rate and asso-ciated mortality while whole-brain irradiation and aggressive chemotherapies are associated with unacceptable toxicity and poor outcome. Thus, new strategies aimed at obtaining durable responses with an acceptable tolerability and reduced risk of neurocognitive decline are needed and these strategies should be tailored not only based on the patients’ age but also on their specific co- morbidities and general health conditions.
For the present trial, all patients aged ≥70 years taken into care at the participating sites will be invited to participate and after informed consent signature their baseline data will be collected in the trial database, including data of patients resulting in screening failure. This will allow to verify any potential screen-ing bias by comparing the characteristics of included and ex-cluded patients. Patients fulfilling the eligibility criteria are then screened for their suitability to receive a more or less aggres-sive anticancer treatment and assigned to two different treat-ment strategies accordingly.
The more fit patients are assigned to the trial Part A and will receive the standard combination of high-dose methotrexate, procarbazine and rituximab as induction. Responding patients will subsequently be randomized to receive either procarbazine or lenalidomide as maintenance therapy. The more fragile pa-tients are assigned to the trial Part B and will receive a less aggressive therapy consisting of concomitant whole-brain radiotherapy, temozolomide and rituximab as induction therapy, followed by temozolomide single-agent as maintenance treatment.
|type of project||clinical studies|
|start of project||2019|
|end of project||2024|
|study design||Phase II|
|responsible person||Felicitas Hitz|