Study: NCT03495960

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Methotrexate
Description: During the primary chemo-immunotherapy (PRIMAIN regimen, 2 courses; every 43 days) administered as induction in the PART A of the study, Methotrexate is given 3 g/m2 as infusion (0.5 g/m2 in 15 min. + 2.5 g/m2 in 3-hr infusion) on days 2, 16 \& 30

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Methotrexate
Description: During the primary chemo-immunotherapy (PRIMAIN regimen, 2 courses; every 43 days) administered as induction in the PART A of the study, Methotrexate is given 3 g/m2 as infusion (0.5 g/m2 in 15 min. + 2.5 g/m2 in 3-hr infusion) on days 2, 16 \& 30

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Procarbazine
Description: PART A - INDUCTION PHASE During the primary chemo-immunotherapy (PRIMAIN regimen, 2 courses; every 43 days) administered as induction in the PART A of the study, Procarbazine is given oral 60 mg/m2/d from days 2 to 11~PART A - MANTEINANCE PHASE (control arm) Patients responsive or with stable disease after two courses of PRIMAIN regimen (the induction treatment) will be randomly allocated to receive two different maintenance therapies. Maintenance will start on day 60 of the 2nd PRIMAIN course.~Procarbazine represents the control arm and is given oral 100 mg/d from day 1 to 5 for 6 courses, every 4 weeks.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Procarbazine
Description: PART A - INDUCTION PHASE During the primary chemo-immunotherapy (PRIMAIN regimen, 2 courses; every 43 days) administered as induction in the PART A of the study, Procarbazine is given oral 60 mg/m2/d from days 2 to 11~PART A - MANTEINANCE PHASE (control arm) Patients responsive or with stable disease after two courses of PRIMAIN regimen (the induction treatment) will be randomly allocated to receive two different maintenance therapies. Maintenance will start on day 60 of the 2nd PRIMAIN course.~Procarbazine represents the control arm and is given oral 100 mg/d from day 1 to 5 for 6 courses, every 4 weeks.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Lenalidomide
Description: Patients responsive or with stable disease after two courses of PRIMAIN regimen (the induction treatment) will be randomly allocated to receive two different maintenance therapies. Maintenance will start on day 60 of the 2nd PRIMAIN course.~Lenalidomide represents the experimental arm and is given oral 25 mg/d from day 1 to 21 for 24 courses; every 4 weeks.

Intervention type: RADIATION
Group type: OTHER
Intervention: Radiotherapy
Description: Patients ineligible for high-dose methotrexate, will be assigned to receive concomitant whole brain radiotherapy-temozolomide-rituximab (Induction Part B). Whole-brain will be irradiated by two opposite lateral fields including the first two cervical vertebras and the posterior two thirds of the eyes. Photons of 4 - 10 MeV, 180 - 200 cGy per day, 5 weekly fractions will be employed

Intervention type: DRUG
Group type: OTHER
Intervention: Temozolomide
Description: PART B - INDUCTION PHASE Patients ineligible for high-dose methotrexate, will be assigned to receive concomitant whole brain radiotherapy-temozolomide-rituximab (Induction Part B). Temoyolomide is given 75 mg/m2/d, every day for the whole duration of radiotherapy.~PART B - MAINTENANCE PHASE Temozolomide is also given as maintenance in Part B. The treatment consists of 12 courses where temozolomide is administered on days 1-5, every 4 weeks at a dose of 150 mg/m2/d at the first course, and of 200 mg/m2/d at the subsequent courses,